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1.
  • Hansson, Björn, et al. (författare)
  • Adipose cell size changes are associated with a drastic actin remodeling
  • 2019
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Adipose tissue plays a major role in regulating whole-body insulin sensitivity and energy metabolism. To accommodate surplus energy, the tissue rapidly expands by increasing adipose cell size (hypertrophy) and cell number (hyperplasia). Previous studies have shown that enlarged, hypertrophic adipocytes are less responsive to insulin, and that adipocyte size could serve as a predictor for the development of type 2 diabetes. In the present study, we demonstrate that changes in adipocyte size correlate with a drastic remodeling of the actin cytoskeleton. Expansion of primary adipocytes following 2 weeks of high-fat diet (HFD)-feeding in C57BL6/J mice was associated with a drastic increase in filamentous (F)-actin as assessed by fluorescence microscopy, increased Rho-kinase activity, and changed expression of actin-regulating proteins, favoring actin polymerization. At the same time, increased cell size was associated with impaired insulin response, while the interaction between the cytoskeletal scaffolding protein IQGAP1 and insulin receptor substrate (IRS)-1 remained intact. Reversed feeding from HFD to chow restored cell size, insulin response, expression of actin-regulatory proteins and decreased the amount of F-actin filaments. Together, we report a drastic cytoskeletal remodeling during adipocyte expansion, a process which could contribute to deteriorating adipocyte function.
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2.
  • Hofvander, Jakob, et al. (författare)
  • Frequent low-level mutations of protein kinase D2 in angiolipoma
  • 2017
  • Ingår i: Journal of Pathology. - : WILEY. - 0022-3417 .- 1096-9896. ; 241:5, s. 578-582
  • Tidskriftsartikel (refereegranskat)abstract
    • Tumours displaying differentiation towards normal fat constitute the most common subgroup of soft tissue neoplasms. A series of such tumours was investigated by whole-exome sequencing followed by targeted ultra-deep sequencing. Eighty per cent of angiolipomas, but not any other tumour type, displayed mutations in the protein kinase D2 (PRKD2) gene, typically in the part encoding the catalytic domain. The absence of other aberrations at the chromosome or RNA level suggests that PRKD2 mutations are critical for angiolipoma development. Consistently, the mutated PRKD2 alleles were present at low (3-15%) frequencies, indicating that only a subset of the tumour cells is affected. Indeed, by sequencing mature fat cells and other cells separately, the former typically showed the highest mutation frequencies. Thus, we hypothesize that altered PRKD2 signalling in the adipocytic cells drives tumourigenesis and, in agreement with its pivotal role in angiogenesis, induces the vessel formation that is characteristic for angiolipoma. Copyright (c) 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley amp; Sons, Ltd.
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3.
  • Kotowska, Dorota, et al. (författare)
  • Short-term lingonberry feeding is associated with decreased insulin levels and altered adipose tissue function in high-fat diet fed C57BL/6J mice
  • 2022
  • Ingår i: Journal of Functional Foods. - : Elsevier BV. - 1756-4646. ; 94, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Intact adipose tissue function is essential to maintain glucose and lipid homeostasis. To study the impact of altered adipose tissue function on whole-body metabolism, diet-induced obesity in mice is frequently used as a model organism. In the current study, we have examined health-promoting effects of a lingonberry supplemented diet. We found C57BL/6J mice fed a high-fat diet supplemented with lingonberry for 4 days to have significantly lowered body-weight gain, adipose tissue expansion, and reduced insulin levels, compared to mice fed an isocaloric high-fat diet. RNA-Seq analysis of epididymal adipose tissue revealed differential expression of genes related to mitochondria fission (Mief1, Dnm1, Vps35, and Opa1). Further, we detected increased gene expression and phosphorylation of perilipin-1 (pS522), and increased lipolysis in primary adipocytes from lingonberry-fed mice. Together, these data pinpoint that beneficial effects of a lingonberry enriched diet are rapidly detectable and that the adipose tissue constitutes a target for these effects.
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4.
  • Söndergaard Hansen, Jesper, et al. (författare)
  • Perilipin 1 binds to aquaporin 7 in human adipocytes and controls its mobility via protein kinase A mediated phosphorylation
  • 2016
  • Ingår i: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495. ; 65:12, s. 1731-1742
  • Tidskriftsartikel (refereegranskat)abstract
    • Accumulating evidence suggests that dysregulated glycerol metabolism contributes to the pathophysiology of obesity and type 2 diabetes. Glycerol efflux from adipocytes is regulated by the aquaglyceroporin AQP7, which is translocated upon hormone stimulation. Here, we propose a molecular mechanism where the AQP7 mobility in adipocytes is dependent on perilipin 1 and protein kinase A. Biochemical analyses combined with ex vivo studies in human primary adipocytes, demonstrate that perilipin 1 binds to AQP7, and that catecholamine activated protein kinase A phosphorylates the N-terminus of AQP7, thereby reducing complex formation. Together, these findings are indicative of how glycerol release is controlled in adipocytes, and may pave the way for the future design of drugs against human metabolic pathologies.
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5.
  • Ahmed, Fozia (författare)
  • Estrogen and its receptors in adipose tissue from women and men : Associations with age, adiposity and type 2 diabetes
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Obesity and its complications, such as insulin resistance and type 2 diabetes (T2D), are leading causes of morbidity and mortality globally. Adipose tissue is important for whole-body homeostasis, functioning as an energy storage reservoir and an endocrine organ. Estrogens mediate their effects through estrogen receptor alpha (ESR1) and beta (ESR2) and contribute to sex and menopause-related differences in body fat distribution. Moreover, estrogens can be produced from androgens in the adipose tissue by the enzyme aromatase. The overall aim of this thesis was to investigate the role of estrogen and estrogen signalling in human adipose tissue and their association with age, adiposity, and insulin resistance. In Paper I, we assessed ESR1 and ESR2 gene expression in subcutaneous adipose tissue (SAT) from pre- and postmenopausal women, and investigated the effects of estradiol on adipocyte glucose uptake. We found that ESR2 gene expression was higher in postmenopausal women than premenopausal women. Moreover, in late, but not pre- or early postmenopausal women, estradiol incubation reduced basal and insulin-stimulated glucose uptake, which corresponded to an increase in ESR2 gene expression levels. The inhibiting effect of estradiol on adipocyte glucose uptake was prevented using an ESR2 antagonist. Subsequently, in Paper II we assessed the role of ESR2 in SAT lipid and glucose metabolism and preadipocyte differentiation. ESR2 expression in SAT was inversely correlated with markers of central adiposity and positively correlated with markers of lipid accumulation. Moreover, ESR2 knockdown impaired subcutaneous preadipocyte differentiation and glucose utilization. In Paper III, we focused on adipocyte lipolysis in women, which is regulated, in part, by catecholamines. OCT3, which mediates catecholamine transport into adipocytes, where they can be degraded, was increased in SAT with age, and higher in postmenopausal women than premenopausal women. Moreover, its expression was negatively associated with markers of insulin resistance and ex vivo lipolysis. Estradiol incubation of SAT downregulated OCT3 gene expression, which may explain lower OCT3 gene expression in premenopausal compared to postmenopausal women. In Paper IV, we focused on the role of aromatase and estradiol in SAT from men. We found that aromatase expression was higher in SAT from men with obesity and T2D compared to subjects without obesity and T2D, respectively, and was positively associated with markers of central obesity and markers of insulin resistance. Contrastingly, ESR1 expression in SAT was lower in men with obesity and T2D compared to subjects without obesity and T2D, respectively, and negatively associated with markers of obesity and insulin resistance. ESR2 expression was higher in SAT from men with T2D compared to men without T2D. Estradiol reduced insulin-stimulated glucose uptake, however, neither testosterone, nor aromatase inhibition, altered adipocyte glucose uptake. In this thesis, we found that estrogen has important metabolic effects in adipose tissue, including regulating lipid accumulation, glucose uptake capacity, and catecholamine transport. Overall, our findings suggest that estrogen and estrogen receptors may have an important role in age-, menopausal- and sex-dependent differences in body fat distribution, and may serve as potential targets for the prevention and treatment obesity and insulin resistance. 
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6.
  • Andersson, Martin, et al. (författare)
  • Jobbskapande och produktivitet i små kontra nya företag : Global Award for Entrepreneurship Research 2020 till John Haltiwanger
  • 2021
  • Ingår i: Ekonomisk Debatt. - : Nationalekonomiska Föreningen. - 0345-2646. ; 7:49, s. 5-15
  • Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
    • Denna artikel presenterar 2020 års pristagare av Global Award for Entrepreneurship Research – John Haltiwanger – och de bidrag han har gjort inom entreprenörskapsforskningen. Haltiwanger har bl a bidragit till att förbättra vår förståelse av hur jobb skapas och försvinner, kartlägga vilka faktorer som styr produktivitet samt analysera hur småföretag bidrar till den ekonomiska utvecklingen. Hans forskning har inspirerat såväl policydebatt som nationella statistikmyndigheter världen över. 
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7.
  • Bennet, Louise, et al. (författare)
  • BMI and waist circumference cut-offs for corresponding levels of insulin sensitivity in a Middle Eastern immigrant versus a native Swedish population - The MEDIM population based study
  • 2016
  • Ingår i: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 16:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The aim of this study was to identify corresponding body mass index (BMI) and waist circumference cut-offs for equivalent levels of insulin sensitivity in a Middle Eastern immigrant population compared with native Swedes. Methods: Citizens of Malmö, Sweden aged 30 to 75 years, who were born in Iraq or Sweden, were in 2010-2012 invited to participate in a health examination including anthropometrics, oral glucose tolerance test, fasting samples and interviews concerning sociodemographic factors and lifestyle behaviours. Results: In total, 1176 individuals born in Iraq and 688 born in Sweden, without previously diagnosed type 2 diabetes, participated in the study. In normal weight participants (BMI < 25 kg/m2), 21.2% of Iraqis vs 9.3% of Swedes were insulin resistant. Corresponding figures in participants without abdominal obesity (waist circumference, men < 94 cm, women < 80 cm) were 28.2% of Iraqis vs 9.4% of Swedes. The age-adjusted insulin sensitivity index (ISI) for obese Swedes (BMI 30 kg/m2) corresponded in Iraqi men with BMI of 28.5 kg/m2, and in Iraqi women with BMI of 27.5 kg/m2. The ISI level in abdominally obese Swedes corresponded with waist circumference cut-offs of 84.0 cm and 71.0 cm in Iraqi men and women, respectively. In men only, larger waist circumference (P interaction = 0.026) presented a stronger association with impaired ISI in Iraqis as compared to Swedes. Conclusions: Our data shows that the impact of BMI and waist circumference on ISI is ethnic- and gender-specific, indicating a disturbed fat metabolism in Iraqi males in particular. Our data suggests that 10 cm lower cut-off values for abdominal obesity, than is currently recommended by major organisations, should be considered when estimating diabetes risk in Middle Eastern populations.
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8.
  • Bergqvist, Niclas, et al. (författare)
  • A systems biology analysis connects insulin receptor signaling with glucose transporter translocation in rat adipocytes
  • 2017
  • Ingår i: Journal of Biological Chemistry. - : AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC. - 1083-351X .- 0021-9258. ; 292:27, s. 11206-11217
  • Tidskriftsartikel (refereegranskat)abstract
    • Type 2 diabetes is characterized by insulin resistance, which arises from malfunctions in the intracellular insulin signaling network. Knowledge of the insulin signaling network is fragmented, and because of the complexity of this network, little consensus has emerged for the structure and importance of the different branches of the network. To help overcome this complexity, systems biology mathematical models have been generated for predicting both the activation of the insulin receptor (IR) and the redistribution of glucose transporter 4 (GLUT4) to the plasma membrane. Although the insulin signal transduction between IR and GLUT4 has been thoroughly studied with modeling and time-resolved data in human cells, comparable analyses in cells from commonly used model organisms such as rats and mice are lacking. Here, we combined existing data and models for rat adipocytes with new data collected for the signaling network between IR and GLUT4 to create a model also for their interconnections. To describe all data (>140 data points), the model needed three distinct pathways from IR to GLUT4: (i) via protein kinase B (PKB) and Akt substrate of 160 kDa (AS160), (ii) via an AS160-independent pathway from PKB, and (iii) via an additional pathway from IR, e.g. affecting the membrane constitution. The developed combined model could describe data not used for training the model and was used to generate predictions of the relative contributions of the pathways from IR to translocation of GLUT4. The combined model provides a systems-level understanding of insulin signaling in rat adipocytes, which, when combined with corresponding models for human adipocytes, may contribute to model-based drug development for diabetes.
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9.
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10.
  • Coad, Alex, et al. (författare)
  • John Haltiwanger : recipient of the 2020 Global Award for Entrepreneurship Research
  • 2022
  • Ingår i: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913. ; 58:1, s. 15-25
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • The 2020 Global Award for Entrepreneurship Research has been awarded to Professor John Haltiwanger. John Haltiwanger has made significant contributions to the field of entrepreneurship by improving our understanding of job creation and destruction, productivity growth, and the role of small- and medium-sized firms (SMEs) in economic development. He has played a major role in the careful development of large, longitudinal firm-level datasets, and introduced a novel and widely adopted measure of firm growth that addresses previous statistical biases. His work has influenced public policy and national statistical offices around the world. Plain English Summary The winner of the 2020 Global Award for Entrepreneurship Research, John Haltiwanger, has pioneered research showing that it is mainly firm age, not size, that matters for job creation. Through analyzing the relationship between employment, growth, and firms, he has advanced our understanding of how the economy works. He has done this by building new datasets and introducing a new measure of firm growth, solving problems encountered with earlier techniques. His work has also broadened the policy debate on entrepreneurship and inspired people all around the world. From a policy perspective, John Haltiwanger has shown that it is difficult to justify targeted industrial and commercial policies, and if job creation is to be supported, politicians need to target young firms rather than small firms. These important findings from John Haltiwanger's pioneering work have been published in world-class leading academic and scientific journals.
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11.
  • Dalla-Riva, Jonathan, et al. (författare)
  • Discoidal HDL and apoA-I-derived peptides improve glucose uptake in skeletal muscle.
  • 2013
  • Ingår i: Journal of Lipid Research. - 1539-7262. ; 54:5, s. 1275-1282
  • Tidskriftsartikel (refereegranskat)abstract
    • Lipid-free apoA-I and mature spherical HDL have been shown to induce glucose uptake in skeletal muscle. To exploit apoA-I and HDL states for diabetes therapy, further understanding of interaction between muscle and apoA-I is required. This study has examined if nascent discoidal HDL, in which apoA-I attains a different conformation from mature HDL and lipid-free states, could induce muscle glucose uptake and if a specific domain of apoA-I can mediate this effect. Using L6 myotubes stimulated with synthetic reconstituted discoidal HDL (rHDL), we show a glucose uptake effect comparable to insulin. Increased plasma membrane GLUT4 levels in ex vivo rHDL-stimulated myofibers from HA-GLUT4-GFP transgenic mice support this observation. rHDL increased phosphorylation of AMP kinase (AMPK) and acetyl-coA carboxylase (ACC) but not Akt. A survey of domain specific peptides of apoA-I showed that the lipid-free C-terminal 190-243 fragment increases plasma membrane GLUT4, promotes glucose uptake, and activates AMPK signaling but not Akt. This may be explained by changes in α-helical content of 190-243 fragment versus full-length lipid-free apoA-I as assessed by circular dichroism spectroscopy. JLR Discoidal HDL and the 190-243 peptide of apoA-I are potent agonists of glucose uptake in skeletal muscle and the C-terminal α-helical content of apoA-I may be an important determinant of this effect.
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12.
  • Dickson, Elna, et al. (författare)
  • Altered Adipocyte Cell Size Distribution Prior to Weight Loss in the R6/2 Model of Huntington's Disease
  • 2023
  • Ingår i: Journal of Huntington's disease. - 1879-6397. ; 12:3, s. 253-266
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Metabolic alterations contribute to disease onset and prognosis of Huntington's disease (HD). Weight loss in the R6/2 mouse model of HD is a consistent feature, with onset in mid-to-late stage of disease.OBJECTIVE: In the present study, we aimed to investigate molecular and functional changes in white adipose tissue (WAT) that occur at weight loss in R6/2 mice. We further elaborated on the effect of leptin-deficiency and early obesity in R6/2 mice.METHODS: We performed analyses at 12 weeks of age; a time point that coincides with the start of weight loss in our R6/2 mouse colony. Gonadal (visceral) and inguinal (subcutaneous) WAT depot weights were monitored, as well as adipocyte size distribution. Response to isoprenaline-stimulated glycerol release and insulin-stimulated glucose uptake in adipocytes from gonadal WAT was assessed.RESULTS: In R6/2 mice, WAT depot weights were comparable to wildtype (WT) mice, and the response to insulin and isoprenaline in gonadal adipocytes was unaltered. Leptin-deficient R6/2 mice exhibited distinct changes compared to leptin-deficient WT mice. At 12 weeks, female leptin-deficient R6/2 mice had reduced body weight accompanied by an increased proportion of smaller adipocytes, while in contrast; male mice displayed a shift towards larger adipocyte sizes without a significant body weight reduction at this timepoint.CONCLUSIONS: We here show that there are early sex-specific changes in adipocyte cell size distribution in WAT of R6/2 mice and leptin-deficient R6/2 mice.
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13.
  • Domingo-Espín, Joan, et al. (författare)
  • Dual actions of apolipoprotein A-I on glucose-stimulated insulin secretion and insulin-independent peripheral tissue glucose uptake lead to increased heart and skeletal muscle glucose disposal
  • 2016
  • Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:7, s. 1838-1848
  • Tidskriftsartikel (refereegranskat)abstract
    • Apolipoprotein A-I (apoA-I) of HDL is central to the transport of cholesterol in circulation. ApoA-I also provides glucose control with described in vitro effects of apoA-I on β-cell insulin secretion and muscle glucose uptake. In addition, apoA-I injections in insulin-resistant diet-induced obese (DIO) mice lead to increased glucose-stimulated insulin secretion (GSIS) and peripheral tissue glucose uptake. However, the relative contribution of apoA-I as an enhancer of GSIS in vivo and as a direct stimulator of insulin-independent glucose uptake is not known. Here, DIO mice with instant and transient blockade of insulin secretion were used in glucose tolerance tests and in positron emission tomography analyses. Data demonstrate that apoA-I to an equal extent enhances GSIS and acts as peripheral tissue activator of insulin-independent glucose uptake and verify skeletal muscle as an apoA-I target tissue. Intriguingly, our analyses also identify the heart as an important target tissue for the apoA-I-stimulated glucose uptake, with potential implications in diabetic cardiomyopathy. Explorations of apoA-I as a novel antidiabetic drug should extend to treatments of diabetic cardiomyopathy and other cardiovascular diseases in patients with diabetes.
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14.
  • Edmunds, Shelley J., et al. (författare)
  • A short peptide of the C-terminal class Y helices of apolipoprotein A-I has preserved functions in cholesterol efflux and in vivo metabolic control
  • 2020
  • Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Apolipoprotein A-I (ApoA-I) of high-density lipoprotein (HDL) induces glucose uptake by muscle tissues and stimulates pancreatic insulin secretion, and also facilitates cholesterol transport in circulation, and is explored for anti-diabetic and anti-atherosclerotic treatments. As the better alternative to complex protein–lipid formulations it was recently established that the C-terminal region of the ApoA-I protein singly improves the metabolic control and prevents formation of atherosclerotic plaques. Additional investigations of peptides based on the ApoA-I structure may lead to novel anti-diabetic drugs. We here investigate a short peptide (33mer, RG33) that corresponds to the two last helical segments (aa 209–241) of the ApoA-I structure (so-called class Y-helices which forms amphipathic helices) for stability and solubility in serum, for in vitro cholesterol efflux capability, and for providing in vivo glucose control in an insulin resistant mouse model. The RG33 peptide efficiently solubilizes lipid-vesicles, and promotes the efflux of cholesterol from cultured macrophages. The efflux capacity is significantly increased in the presence of lipids compared to non-lipidated RG33. Finally, acute treatment with the RG33 peptide significantly improves the glucose clearance capacity of insulin resistant mice. The impact of the RG33 peptide on glucose control and cholesterol transport, as well as the physicochemical properties, makes it a good candidate for translational exploration of its therapeutic potential in diabetes treatment.
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15.
  • Edmunds, Shelley J, et al. (författare)
  • ApoAI-derived peptide increases glucose tolerance and prevents formation of atherosclerosis in mice
  • 2019
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 62:7, s. 1257-1267
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: Finding new treatment alternatives for individuals with diabetes with severe insulin resistance is highly desired. To identify novel mechanisms that improve glucose uptake in skeletal muscle, independently from insulin levels and signalling, we have explored the therapeutic potential of a short peptide sequence, RG54, derived from apolipoprotein A-I (ApoA-I).METHODS: INS-1E rat clonal beta cells, C2C12 rat muscle myotubes and J774 mouse macrophages were used to study the impact of RG54 peptide on glucose-stimulated insulin secretion, glucose uptake and cholesterol efflux, respectively. GTTs were carried out on diet-induced insulin-resistant and Leprdb diabetic mouse models treated with RG54 peptide, and the impact of RG54 peptide on atherosclerosis was evaluated in Apoe-/- mice. Control mice received ApoA-I protein, liraglutide or NaCl.RESULTS: The synthetic RG54 peptide induced glucose uptake in cultured muscle myotubes by a similar amount as insulin, and also primed pancreatic beta cells for improved glucose-stimulated insulin secretion. The findings were verified in diet-induced insulin-resistant and Leprdb diabetic mice, jointly confirming the physiological effect. The RG54 peptide also efficiently catalysed cholesterol efflux from macrophages and prevented the formation of atherosclerotic plaques in Apoe-/- mice.CONCLUSIONS/INTERPRETATION: The RG54 peptide exhibits good prospects for providing glucose control and reducing the risk of cardiovascular disease in individuals with severe insulin resistance.
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16.
  • Erlanson-Albertsson, Charlotte, et al. (författare)
  • The importance of food for endotoxemia and an inflammatory response
  • 2021
  • Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 22:17
  • Forskningsöversikt (refereegranskat)abstract
    • Bacterial endotoxin is a potent inflammatory antigen abundant in the human intestine. Endotoxins circulate in the blood at low concentrations in all healthy individuals. Elevated levels of circulatory endotoxins may cause inflammation with the development of chronic disease, either affecting metabolism, neurological disease, or resistance to viral and bacterial infections. The most important endotoxin is LPS, being a superantigen. In this narrative review, the effect of various food components to postprandially elevate circulating LPS and inflammatory markers is described. There is evidence that the intake of food enriched in fat, in particular saturated fat, may elevate LPS and pro-inflammatory markers. This occurs in both normal-weight and obese subjects. In obese subjects, inflammatory markers are already elevated before meal consumption. The importance of food choice for endotoxemia and inflammatory response is discussed.
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17.
  • Fex, Malin, et al. (författare)
  • Serotonin and adipocyte function
  • 2019
  • Ingår i: Serotonin : The Mediator that Spans Evolution - The Mediator that Spans Evolution. - 9780128000502 ; , s. 197-202
  • Bokkapitel (refereegranskat)abstract
    • The ability to store and mobilize energy is fundamental for physiologic function. Most excess energy is stored in adipose tissue as triglycerides, which is released as free fatty acids when needed through cellular processes tightly regulated by insulin. Intact adipose cell function is essential to regulate whole-body glucose and lipid metabolism. Several studies have focused on the metabolic impact of 5-hydroxytryptamine (5-HT) on lipid metabolism and glucose homeostasis, and it has been demonstrated that circulating 5-HT, through different routes of action, exerts adipocyte-specific effects that influence both lipid- and glucose metabolism as well as cytokine secretion.
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18.
  • Foss, Nicolai J., et al. (författare)
  • Saras Sarasvathy : recipient of the 2022 Global Award for Entrepreneurship Research
  • 2023
  • Ingår i: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913. ; 61:1, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Professor Saras Sarasvathy is the recipient of the 2022 Global Award for Entrepreneurship Research. Her research contributions have fundamentally changed and invigorated the conversation in the domain of entrepreneurship research. Sarasvathy’s work on effectuation emphasizes how entrepreneurs operate based on available resources, think in terms of affordable loss rather than profit maximization, leverage trustworthy partnerships, and treat unforeseen contingencies as opportunities rather than problems. It has led and inspired a new generation of researchers in the quest for a better understanding of how entrepreneurs make their decisions and the unfolding of the entrepreneurial process. © 2023, The Author(s).
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19.
  • Foss, Nicolai J., et al. (författare)
  • Saras Sarasvathy : recipient of the 2022 Global Award for Entrepreneurship Research
  • 2023
  • Ingår i: Small Business Economics. - : Springer. - 0921-898X .- 1573-0913. ; 61, s. 1-10
  • Tidskriftsartikel (populärvet., debatt m.m.)abstract
    • Professor Saras Sarasvathy is the recipient of the 2022 Global Award for Entrepreneurship Research. Her research contributions have fundamentally changed and invigorated the conversation in the domain of entrepreneurship research. Sarasvathy's work on effectuation emphasizes how entrepreneurs operate based on available resources, think in terms of affordable loss rather than profit maximization, leverage trustworthy partnerships, and treat unforeseen contingencies as opportunities rather than problems. It has led and inspired a new generation of researchers in the quest for a better understanding of how entrepreneurs make their decisions and the unfolding of the entrepreneurial process.
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20.
  • Franck, Niclas, et al. (författare)
  • Insulin-induced GLUT4 translocation to the plasma membrane is blunted in large compared with small primary fat cells isolated from the same individual
  • 2007
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:8, s. 1716-1722
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims/hypothesis: Several studies have suggested that large fat cells are less responsive to insulin than small fat cells. However, in these studies, large fat cells from obese individuals were compared with smaller fat cells from leaner participants, in effect making it impossible to draw conclusions about whether there is a causal relationship between fat cell size and insulin sensitivity. We hypothesised that small fat cells might be more insulin-responsive than large adipocytes when obtained from the same individual. Materials and methods: We developed a method of sorting isolated primary human fat cells by using nylon filters of two different pore sizes. The cells were stained to visualise DNA, which allowed discrimination from artefacts such as lipid droplets. The sorted cells were left to recover overnight, since we had previously demonstrated that this is necessary for correct assessment of insulin response. Results: We found similar amounts of the insulin receptor (IR), IRS-1 and GLUT4 when we compared small and large adipocytes from the same volunteer by immunoblotting experiments using the same total cell volume from both cell populations. Activation of IR, IRS-1 and Akt1 (also known as protein kinase B) by insulin was similar in the two cell populations. However, immunofluorescence confocal microscopy of plasma membrane sheets did not reveal any increase in the amount of GLUT4 in the plasma membrane following insulin stimulation in the large fat cells, whereas we saw a twofold increase in the amount of GLUT4 in the small fat cells. Conclusions/interpretation: Our results support a causal relationship between the accumulation of large fat cells in obese individuals and reduced insulin responsiveness.
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21.
  • Fryklund, Claes, et al. (författare)
  • Adipocyte traits limiting cellular insulin responsiveness and glucose transport
  • 2023
  • Ingår i: American Journal of Physiology - Endocrinology and Metabolism. - 1522-1555. ; 325:6, s. 682-687
  • Tidskriftsartikel (refereegranskat)abstract
    • Adipocyte dysfunction is a hallmark of systemic insulin resistance. Insulin-responsive glucose transporter 4 (GLUT4) is downregulated in the insulin resistant state, and cellular insulin responsiveness varies depending on fat-depot origin and degree of adipose expansion. Here, we have resolved factors limiting cellular insulin responsiveness, by examining adipocyte function and traits related to glucose transport at the cellular level. Subcutaneous (inguinal) and visceral (epididymal) adipocytes were isolated from C57BL/6J mice fed either chow or high-fat diet. Cell-size was determined using coulter counter method, glucose uptake and cytosolic volume were assessed using glucose-tracer assays. Total and GLUT4 protein content expression were determined by western blot. We found that basal glucose uptake per cell was preserved independent of diet or fat depot origin. Insulin-stimulated glucose uptake per cell was sustained in visceral adipocytes but decreased with adipose expansion in subcutaneous adipocytes. In parallel, the cytosolic space and total protein increased proportionally to total cellular volumetric expansion in visceral, but not subcutaneous, adipocytes, while GLUT4 content decreased exclusively in expanding subcutaneous adipocytes. Together, these data support the existence of distinct phenotypic adipocyte traits that could limit cellular insulin responsiveness. Potentially, these characteristics account for fat depot-specific differences related to glucose transport capacity.
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22.
  • Fryklund, Claes, et al. (författare)
  • EH Domain-Containing 2 Deficiency Restricts Adipose Tissue Expansion and Impairs Lipolysis in Primary Inguinal Adipocytes
  • 2021
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Lipid uptake can be facilitated via caveolae, specific plasma membrane invaginations abundantly expressed in adipocytes. The dynamin-related protein EH domain-containing 2 (EHD2) stabilizes caveolae at the cell surface. Here, we have examined the importance of EHD2 for lipid handling using primary adipocytes isolated from EHD2 knockout (Ehd2−/−) C57BL6/N mice. Following high-fat diet (HFD) feeding, we found a clear impairment of epididymal, but not inguinal, adipose tissue expansion in Ehd2−/− compared with Ehd2+/+ (WT) mice. Cell size distribution analysis revealed that Ehd2−/− mice had a lower proportion of small adipocytes, and an accumulation of medium-sized adipocytes in both epididymal and inguinal adipose tissue. Further, PPARγ activity, FABP4 and caveolin-1 expression were decreased in adipocytes isolated from Ehd2−/− mice. Inguinal adipocytes isolated from Ehd2−/− mice displayed reduced lipolysis in response to beta adrenergic receptor agonist, which was associated with reduced phosphorylation of perilipin-1 and hormone sensitive lipase (HSL). This impairment could not be rescued using a cAMP analog, indicating that impaired lipolysis in Ehd2−/− primary adipocytes likely occurs at the level of, or downstream of, protein kinase A (PKA). Altogether, these findings pinpoint the importance of EHD2 for maintained intracellular lipid metabolism, and emphasize differences in mechanisms regulating lipid handling in various adipose-tissue depots.
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23.
  • Fryklund, Claes, et al. (författare)
  • Expansion of the Inguinal Adipose Tissue Depot Correlates With Systemic Insulin Resistance in C57BL/6J Mice
  • 2022
  • Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • To accommodate surplus energy, the adipose tissue expands by increasing adipocyte size (hypertrophy) and number (hyperplasia). The presence of hypertrophic adipocytes is a key characteristic of adipose tissue dysfunction. High-fat diet (HFD) fed C57BL/6J mice are a commonly used model to study obesity and obesity-related complications. In the present study, we have characterized adipose plasticity, at both the cellular and tissue level, by examining the temporal development of systemic insulin resistance and adiposity in response to HFD-feeding for 4, 8, and 12 weeks (4w, 8w, and 12w). Within the same time frame, we examined systemic metabolic flexibility and adipose plasticity when switching from HFD- to chow-diet during the last 2 weeks of diet intervention (referred to as the reverse (REV) group: 4wREV (2w HFD+2w chow), 8wREV (6w HFD+2w chow), 12wREV (10w HFD+2w chow)). In response to HFD-feeding over time, the 12w group had impaired systemic insulin sensitivity compared to both the 4w and 8w groups, accompanied by an increase in hypertrophic inguinal adipocytes and liver triglycerides. After reversing from HFD- to chow-feeding, most parameters were completely restored to chow control levels for 4wREV and 8wREV groups. In contrast, the 12wREV group had a significantly increased number of hypertrophic adipocytes, liver triglycerides accumulation, and impaired systemic insulin sensitivity compared to chow-fed mice. Further, image analysis at the single-cell level revealed a cell-size dependent organization of actin filaments for all feeding conditions. Indeed, the impaired adipocyte size plasticity in the 12wREV group was accompanied by increased actin filamentation and reduced insulin-stimulated glucose uptake compared with chow-fed mice. In summary, these results demonstrate that the C57BL/6J HFD-feeding model has a large capacity to restore adipocyte cell size and systemic insulin sensitivity, and that a metabolic tipping point occurs between 8 and 12w of HFD-feeding where this plasticity deteriorates. We believe these findings provide substantial understanding of C57BL/6J mice as an obesity model, and that an increased pool of hypertrophic ING adipocytes could contribute to aggravated insulin resistance.
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24.
  • Fryklund, Claes, et al. (författare)
  • Impaired glucose transport in inguinal adipocytes after short-term high-sucrose feeding in mice
  • 2020
  • Ingår i: Journal of Nutritional Biochemistry. - : Elsevier BV. - 0955-2863. ; 78
  • Tidskriftsartikel (refereegranskat)abstract
    • Diets enriched in sucrose severely impair metabolic regulation and are associated with obesity, insulin resistance and glucose intolerance. In the current study, we investigated the effect of 4 weeks high-sucrose diet (HSD) feeding in C57BL6/J mice, with specific focus on adipocyte function. Mice fed HSD had slightly increased adipose tissue mass but displayed similar hepatic triglycerides, glucose and insulin levels, and glucose clearance capacity as chow-fed mice. Interestingly, we found adipose depot-specific differences, where both the non- and insulin-stimulated glucose transports were markedly impaired in primary adipocytes isolated from the inguinal fat depot from HSD-fed mice. This was accompanied by decreased protein levels of both GLUT4 and AS160. A similar but much less pronounced trend was observed in the retroperitoneal depot. In contrast, both GLUT4 expression and insulin-stimulated glucose uptake were preserved in adipocytes isolated from epididymal adipose tissue with HSD. Further, we found a slight shift in cell size distribution towards larger cells with HSD and a significant decrease of ACC and PGC-1α expression in the inguinal adipose tissue depot. Moreover, fructose alone was sufficient to decrease GLUT4 expression in cultured, mature adipocytes. Altogether, we demonstrate that short-term HSD feeding has deleterious impact on insulin response and glucose transport in the inguinal adipose tissue depot, specifically. These changes occur before the onset of systemic glucose dysmetabolism and therefore could provide a mechanistic link to overall impaired energy metabolism reported after prolonged HSD feeding, alone or in combination with HFD.
  •  
25.
  • Fryklund, Claes, et al. (författare)
  • Rosiglitazone treatment enhances intracellular actin dynamics and glucose transport in hypertrophic adipocytes
  • 2022
  • Ingår i: Life Sciences. - : Elsevier BV. - 0024-3205. ; 299
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: To accommodate surplus energy, adipose tissue expands by increasing both adipose cell size (hypertrophy) and cell number (hyperplasia). Enlarged, hypertrophic adipocytes are known to have reduced insulin response and impaired glucose transport, which negatively influence whole-body glucose homeostasis. Rosiglitazone is a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, known to stimulate hyperplasia and to efficiently improve insulin sensitivity. Still, a limited amount of research has investigated the effects of rosiglitazone in mature, hypertrophic adipocytes. Therefore, the objective of this study was to examine rosiglitazone's effect on insulin-stimulated glucose uptake in hypertrophic adipocytes. Main methods: C57BL/6J male mice were subjected to 2 weeks of high-fat diet (HFD) followed by 1 week of HFD combined with daily administration of rosiglitazone (10 mg/kg). Adipose cell-size distribution and gene expression were analysed in intact adipose tissue, and glucose uptake, insulin response, and protein expression were examined using primary adipocytes isolated from epididymal and inguinal adipose tissue. Key findings: HFD-feeding induced an accumulation of hypertrophic adipocytes, which was not affected by rosiglitazone-treatment. Still, rosiglitazone efficiently improved insulin-stimulated glucose transport without restoring insulin signaling or GLUT4 expression in similar-sized adipocytes. This improvement occurred concurrently with extracellular matrix remodelling and restored intracellular levels of targets involved in actin turnover. Significance: These results demonstrate that rosiglitazone improves glucose transport in hypertrophic adipocytes, and highlights the importance of the cytoskeleton and extracellular matrix as potential therapeutic targets.
  •  
26.
  • Hansson, Björn, et al. (författare)
  • A hypothesis for insulin resistance in primary human adipocytes involving MRTF-A and suppression of PPARγ
  • 2020
  • Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 533:1, s. 64-69
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is the main risk factor behind insulin resistance and type 2 diabetes. Still, the mechanism behind adipocyte dysfunction is not yet resolved. Recently, we reported that rapid actin remodeling correlates with adipose cell size changes after short-term overfeeding. Therefore, we hypothesized that the actin-driven myocardin-related transcription factor (MRTF-A) contributes to impaired mature adipocyte function. Primary human adipocytes were subjected to adenoviral overexpression of MRTF-A or MRTF-B, followed by Western blot analysis and tracer glucose uptake assay. Further, we assessed cell size distribution, insulin response, MRTF-A localization, actin organization and degree of polymerization in adipocytes isolated from Ob/Ob mice. Overexpression of MRTF-A, but not MRTF-B, markedly suppressed PPARγ expression. Further, MRTF-A expression resulted in decreased IRS-1 level, shifted phosphorylation of Akt (pS473/pT308), IRS-1 (pS302) and AS160 (pT642), and lowered insulin-stimulated glucose uptake. Hypertrophic adipocytes from Ob/Ob mice displayed an increased proportion of polymerized actin, and increased nuclear translocation of MRTF-A compared with control (Ob/+). Similar with human adipocytes overexpressing MRTF-A, adipocytes isolated from Ob/Ob mice had reduced expression of IRS-1 and PPARγ, as well as impaired insulin response. Together, these data demonstrate that MRTF-A negatively influences insulin sensitivity and the expression of key targets in fully mature human adipocytes. This suggests that MRTF-A is poised to exert a transcriptional response in hypertrophic adipocytes, contributing to adipocyte dysfunction and insulin resistance.
  •  
27.
  • Hansson, Björn, et al. (författare)
  • Intact glucose uptake despite deteriorating signaling in adipocytes with high-fat feeding
  • 2018
  • Ingår i: Journal of Molecular Endocrinology. - 0952-5041. ; 60:3, s. 199-211
  • Tidskriftsartikel (refereegranskat)abstract
    • To capture immediate cellular changes during diet-induced expansion of adipocyte cell volume and number, we characterized mature adipocytes during a short-term high-fat diet (HFD) intervention. Male C57BL6/J mice were fed chow diet, and then switched to HFD for 2, 4, 6 or 14 days. Systemic glucose clearance was assessed by glucose tolerance test. Adipose tissue was dissected for RNA-seq and cell size distribution analysis using coulter counting. Insulin response in isolated adipocytes was monitored by glucose uptake assay and Western blotting, and confocal microscopy was used to assess autophagic activity. Switching to HFD was accompanied by an immediate adipocyte size expansion and onset of systemic insulin resistance already after two days, followed by recruitment of new adipocytes. Despite an initially increased non-stimulated and preserved insulin-stimulated glucose uptake, we observed a decreased phosphorylation of insulin receptor substrate-1 (IRS-1) and protein kinase B (PKB). After 14 days of HFD, both the insulin-stimulated phosphorylation of Akt substrate of 160 kDa (AS160) and glucose uptake was blunted. RNA-seq analysis of adipose tissue revealed transient changes in gene expression at day four, including highly significant upregulation of Trp53inp, previously demonstrated to be involved in autophagy. We confirmed increased autophagy, measured as an increased density of LC3-positive puncta and decreased p62 expression after 14 days of HFD. In conclusion, HFD rapidly induced systemic insulin resistance, whereas insulin-stimulated glucose uptake remained intact throughout 6 days of HFD feeding. We also identified autophagy as an early cellular process that potentially influences adipocyte function upon switching to HFD.
  •  
28.
  • Hansson, Björn, et al. (författare)
  • Rosiglitazone drives cavin-2/SDPR expression in adipocytes in a CEBPα-dependent manner
  • 2017
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:3
  • Tidskriftsartikel (refereegranskat)abstract
    • Caveolae are abundant adipocyte surface domains involved in insulin signaling, membrane trafficking and lipid homeostasis. Transcriptional control mechanisms for caveolins and cavins, the building blocks of caveolae, are thus arguably important for adipocyte biology and studies in this area may give insight into insulin resistance and diabetes. Here we addressed the hypothesis that one of the less characterized caveolar components, cavin-2 (SDPR), is controlled by CCAAT/Enhancer Binding Protein (CEBPα) and Peroxisome Proliferator- Activated Receptor Gamma (PPARG). Using human mRNA expression data we found that SDPR correlated with PPARG in several tissues. This was also observed during differentiation of 3T3-L1 fibroblasts into adipocytes. Treatment of 3T3-L1-derived adipocytes with the PPARγ-activator Rosiglitazone increased SDPR and CEBPα expression at both the mRNA and protein levels. Silencing of CEBPα antagonized these effects. Further, adenoviral expression of PPARγ/CEBPα or Rosiglitazone-treatment increased SDPR expression in primary rat adipocytes. The myocardin family coactivator MKL1 was recently shown to regulate SDPR expression in human coronary artery smooth muscle cells. However, we found that actin depolymerization, known to inhibit MKL1 and MKL2, was without effect on SDPR mRNA levels in adipocytes, even though overexpression of MKL1 and MKL2 had the capacity to increase caveolins and cavins and to repress PPARγ/CEBPα. Altogether, this work demonstrates that CEBPα expression and PPARγ-activity promote SDPR transcription and further supports the emerging notion that PPARγ/CEBPα and MKL1/MKL2 are antagonistic in adipocytes.
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29.
  • Hansson, Björn, et al. (författare)
  • Serotonin (5-HT) and 5-HT2A receptor agonists suppress lipolysis in primary rat adipose cells
  • 2016
  • Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 0006-291X. ; 474:2, s. 357-363
  • Tidskriftsartikel (refereegranskat)abstract
    • Serotonin (5-HT) is a biogenic monoamine that functions both as a neurotransmitter and a circulating hormone. Recently, the metabolic effects of 5-HT have gained interest and peripheral 5-HT has been proposed to influence lipid metabolism in various ways. Here, we investigated the metabolic effects of 5-HT in isolated, primary rat adipose cells. Incubation with 5-HT suppressed β-adrenergically stimulated glycerol release and decreased phosphorylation of protein kinase A (PKA)-dependent substrates, hormone sensitive lipase (Ser563) and perilipin (Ser522). The inhibitory effect of 5-HT on lipolysis enhanced the anti-lipolytic effect of insulin, but sustained in the presence of phosphodiesterase inhibitors, OPC3911 and isobuthylmethylxanthine (IBMX). The relative expression of 5-HT1A, -2B and -4 receptor class family were significantly higher in adipose tissue compared to adipose cells, whereas 5-HT1D, -2A and -7 were highly expressed in isolated adipose cells. Similar to 5-HT, 5-HT2 receptor agonists reduced lipolysis while 5-HT1 receptor agonists rather decreased non-stimulated and insulin-stimulated glucose uptake. Together, these data provide evidence of a direct effect of 5-HT on adipose cells, where 5-HT suppresses lipolysis and glucose uptake, which could contribute to altered systemic lipid- and glucose metabolism.
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30.
  • Henrekson, Magnus, et al. (författare)
  • Per Davidsson: 2023 års mottagare av Global Award for Entrepreneurship Research
  • 2023
  • Ingår i: Ekonomisk Debatt. - : Nationalekonomiska Föreningen. - 2002-4231 .- 0345-2646. ; 51:7, s. 18-28
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Professor Per Davidsson är mottagare av 2023 års Global Award for Entrepreneurship Research. Under sin utomordentligt produktiva karriär har han gjort ovärderliga insatser för att bygga upp forskningsområdet entreprenörskap. Hans tidiga studier om entreprenörskap och kultur samt om småföretagens tillväxt spelade en viktig roll för uppkomsten och utvecklingen av entreprenörskap som en vetenskaplig disciplin. Han har också fortlöpande bidragit med mer konceptuella bidrag genom att kritiskt granska utvecklingen av forskningsfältet och genom att skriva grundläggande böcker som har använts flitigt vid högre utbildningsinstitutioner. Genom att undersöka och ifrågasätta traditionella antaganden har han bidragit till att förbättra och förnya området.
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31.
  • Henriksson, Emma, et al. (författare)
  • SIK2 regulates CRTCs, HDAC4 and glucose uptake in adipocytes
  • 2015
  • Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 128:3, s. 472-486
  • Tidskriftsartikel (refereegranskat)abstract
    • Salt-inducible kinase 2 (SIK2) is an AMP-activated protein kinase (AMPK) related kinase abundantly expressed in adipose tissue. Our aim was to identify molecular targets and functions of SIK2 in adipocytes, and to address the role of PKA-mediated phosphorylation of SIK2 on Ser358. Modulation of SIK2 in adipocytes resulted in altered phosphorylation of CREB-regulated transcription co-activator 2 (CRTC2), CRTC3 and class IIa histone deacetylase 4 (HDAC4). Furthermore, CRTC2, CRTC3, HDAC4 and protein phosphatase 2A (PP2A) interacted with SIK2, and the binding of CRTCs and PP2A to wild-type but not Ser358Ala SIK2, was reduced by cAMP elevation. Silencing of SIK2 resulted in reduced GLUT4 (also known as SLC2A4) protein levels, whereas cells treated with CRTC2 or HDAC4 siRNA displayed increased levels of GLUT4. Overexpression or pharmacological inhibition of SIK2 resulted in increased and decreased glucose uptake, respectively. We also describe a SIK2-CRTC2-HDAC4 pathway and its regulation in human adipocytes, strengthening the physiological relevance of our findings. Collectively, we demonstrate that SIK2 acts directly on CRTC2, CRTC3 and HDAC4, and that the cAMP-PKA pathway reduces the interaction of SIK2 with CRTCs and PP2A. Downstream, SIK2 increases GLUT4 levels and glucose uptake in adipocytes.
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32.
  • Herrgårdh, Tilda, et al. (författare)
  • A multi-scale digital twin for adiposity-driven insulin resistance in humans : diet and drug effects
  • 2023
  • Ingår i: Diabetology & Metabolic Syndrome. - : BioMed Central (BMC). - 1758-5996. ; 15:1
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The increased prevalence of insulin resistance is one of the major health risks in society today. Insulin resistance involves both short-term dynamics, such as altered meal responses, and long-term dynamics, such as the development of type 2 diabetes. Insulin resistance also occurs on different physiological levels, ranging from disease phenotypes to organ-organ communication and intracellular signaling. To better understand the progression of insulin resistance, an analysis method is needed that can combine different timescales and physiological levels. One such method is digital twins, consisting of combined mechanistic mathematical models. We have previously developed a model for short-term glucose homeostasis and intracellular insulin signaling, and there exist long-term weight regulation models. Herein, we combine these models into a first interconnected digital twin for the progression of insulin resistance in humans.METHODS: The model is based on ordinary differential equations representing biochemical and physiological processes, in which unknown parameters were fitted to data using a MATLAB toolbox. RESULTS: The interconnected twin correctly predicts independent data from a weight increase study, both for weight-changes, fasting plasma insulin and glucose levels, and intracellular insulin signaling. Similarly, the model can predict independent weight-change data in a weight loss study with the weight loss drug topiramate. The model can also predict non-measured variables.CONCLUSIONS: The model presented herein constitutes the basis for a new digital twin technology, which in the future could be used to aid medical pedagogy and increase motivation and compliance and thus aid in the prevention and treatment of insulin resistance.
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33.
  • Hien, Tran T., et al. (författare)
  • MicroRNA-dependent regulation of KLF4 by glucose in vascular smooth muscle
  • 2018
  • Ingår i: Journal of Cellular Physiology. - : Wiley. - 0021-9541 .- 1097-4652. ; 233:9, s. 7195-7205
  • Tidskriftsartikel (refereegranskat)abstract
    • Diabetes is a major risk factor for cardiovascular disease and this is in part due to the effects of hyperglycemia on vascular smooth muscle cells. Small non-coding microRNAs are known to control smooth muscle phenotype and arterial contractility and are dysregulated in diabetes. The effect of microRNAs on smooth muscle differentiation is in part mediated by the transcription factor KLF4 but the role of this mechanism in diabetic vascular disease is not fully understood. Herein, we have investigated the importance of hyperglycemia and diabetes for the expression of KLF4 in vascular smooth muscle and the involvement of miRNAs in this regulation. Hyperglycemia down-regulated KLF4 in vascular smooth muscle cells and similar results were found in arteries of diabetic mice and patients. This correlated with a Foxa2-dependent up-regulation of miR-29c, which targeted KLF4 in vascular smooth muscle cells. Importantly, by preventing downregulation of KLF4, the induction of smooth muscle contractile protein markers by glucose was inhibited. In conclusion, miR-29 mediated inhibition of KLF4 in hyperglycemic conditions contributes to increased expression of contractile markers in vascular smooth muscle cells. Further studies are warranted to determine the therapeutic implications of miR-29 inhibition in diabetic vascular disease.
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34.
  • Hien Tran, Thi, et al. (författare)
  • Elevated glucose levels promote contractile and cytoskeletal gene expression in vascular smooth muscle via Rho/protein kinase C and actin polymerization.
  • 2016
  • Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 291:7, s. 68-3552
  • Tidskriftsartikel (refereegranskat)abstract
    • Both type 1 and type 2 diabetes are associated with increased risk of cardiovascular disease. This is in part attributed to the effects of hyperglycemia on vascular endothelial and smooth muscle cells but the underlying mechanisms are not fully understood. In diabetic animal models, hyperglycemia results in hyper-contractility of vascular smooth muscle possibly due to increased activation of Rho-kinase. The aim of the present study was to investigate the regulation of contractile smooth muscle markers by glucose and to determine the signaling pathways that are activated by hyperglycemia in smooth muscle cells. Microarray, qPCR and western blot analyses revealed that both mRNA and protein expression of contractile smooth muscle markers was increased in isolated smooth muscle cells cultured under high compared to low glucose conditions. This effect was also observed in hyperglycemic Akita mice and in diabetic patients. Elevated glucose activated the protein kinase C and Rho/Rho-kinase signaling pathways and stimulated actin polymerization. Glucose-induced expression of contractile smooth muscle markers in cultured cells could be partially or completely repressed by inhibitors of advanced glycation end products, L-type calcium channels, protein kinase C, Rho-kinase, actin polymerization and myocardin related transcription factors. Furthermore, genetic ablation of the miR-143/145 cluster prevented the effects of glucose on smooth muscle marker expression. In conclusion, these data demonstrate a possible link between hyperglycemia and vascular disease states associated with smooth muscle contractility.
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35.
  • Holt, Vance, et al. (författare)
  • Acute cytokine treatment stimulates glucose uptake and glycolysis in human keratinocytes
  • 2023
  • Ingår i: Cytokine. - : Elsevier BV. - 1043-4666. ; 161
  • Tidskriftsartikel (refereegranskat)abstract
    • During inflammation, cellular glucose uptake and glycolysis are upregulated to meet an increased energy demand. For example, keratinocyte glycolysis is essential for progression of psoriasis. Therefore, understanding the regulation of glucose metabolism in keratinocytes is of importance. Here, we show that the pro-inflammatory cytokines IFNγ and TNF together rapidly induce glucose uptake, glycolysis, and glycolytic capacity in cultured keratinocytes. Furthermore, we found that acute IFNγ and TNF stimulation induces glucose transporter 4 (GLUT4) translocation to the plasma membrane and engages AMPK-dependent intracellular signaling. Together, these findings suggest acute cytokine-induced glucose metabolism in keratinocytes could contribute to inflammation in psoriatic disease, and that GLUT4 is involved in these processes.
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36.
  • Karlsson, Margareta, 1942-, et al. (författare)
  • Colocalization of insulin receptor and insulin receptor substrate-1 to caveolae in primary human adipocytes
  • 2004
  • Ingår i: European Journal of Biochemistry. - : Wiley. - 0014-2956 .- 1432-1033. ; 271:12, s. 2471-2479
  • Tidskriftsartikel (refereegranskat)abstract
    • Caveolae are plasma membrane invaginations with several functions, one of which appears to be to organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin receptor was localized to caveolae by electron microscopy/immunogold detection and by isolating caveolae from plasma membranes. Part of insulin receptor substrate 1 (IRS1), the immediate downstream signal mediator, was colocalized with the insulin receptor in the plasma membrane and caveolae, as demonstrated by immunofluorescence microscopy, immunogold electron microscopy, and immunogold electron microscopy of transfected recombinant HA-IRS1. In contrast, rat epididymal adipocytes lacked IRS1 at the plasma membrane. Depletion of cholesterol from the cells using β-cyclodextrin blocked insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulin stimulation of protein kinase B and Map-kinases extracellular signal-related kinase (ERK)1/2 phosphorylation. Insulin-stimulated phosphorylation of the insulin receptor and IRS1 was not affected, indicating that caveolae integrity is required downstream of IRS1. In conclusion we show that insulin receptor and IRS1 are both caveolar proteins and that caveolae are required for both metabolic and mitogenic control in human adipocytes. Our results establish caveolae as foci of insulin action and stress the importance of examining human cells in addition to animal cells and cell lines.
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37.
  • Karlsson, Margareta, et al. (författare)
  • In human adipocytes the insulin receptor and IRS1 are localized in caveolae, and caveolae destruction makes cells resistant to insulin signaling for metabolic and mitogenic control
  • Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
    • Caveolae are plasma membrane invaginations with several functions, one of which appears to be to organize receptor mediated sigoaling. Here we show that in human adipocytes the iosulin receptor is localized in caveolae: by electron microscopy and immunogold detection and by isolating caveolae from plasma membranes. We similarly demonstrate that significant part of the immediate downstream signal mediator IRS1 is localized at the plasma membrane and caveolae. A detailed image shows the caveola as a bulb, protroding into the cell interior, with a neck attaching it to the plasma membrane. The caveolar structural protein caveolin is localized in the neck aod not in the bulb of the caveola. The receptor is active in caveolae since insulin stimulation caused tyrosine specific phosphorylation of the receptor recovered in isolated caveolae. Caveolae contain a major part of the free cholesterol in the plasma membrane and cholesterol is a stroctural component of caveolae. Depletion of cholesterol from the cells using B-cyclodextrio blocks insulin stimulation of glucose uptake, insulin inhibition of perilipin phosphorylation in response to isoproterenol, and insulio stimulation of protein kinase B and Map-kinases ERK1/2 phosphorylation- in effect making the human adipocytes insulin resistant. The insulin-stimulated phosphorylation of the insulin receptor and IRS1 are, however, not affected, indicating that caveolae integrity is required downstream of IRS1, consistent with its colocalization with the insulin receptor io caveolae in human adipocytes.
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38.
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39.
  • Lindahl, Maria, et al. (författare)
  • ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation.
  • 2015
  • Ingår i: Journal of Lipid Research. - 1539-7262. ; 56:12, s. 2248-2259
  • Tidskriftsartikel (refereegranskat)abstract
    • ApoA-I, the main protein component of high-density lipoprotein (HDL), is suggested to be involved in metabolic homeostasis. We examined the effects of Milano, a naturally occurring ApoA-I variant, about which little mechanistic information is available. Remarkably, high fat-fed mice treated with Milano displayed a rapid weight loss greater than ApoA-I WT treated mice, and a significantly reduced adipose tissue mass, without an inflammatory response. Further, lipolysis in adipose cells isolated from mice treated with either WT or Milano was increased. In primary rat adipose cells, Milano stimulated cholesterol efflux and increased glycerol release, independently of β-adrenergic stimulation and phosphorylation of hormone sensitive lipase (Ser563) and perilipin (Ser522). Stimulation with Milano had a significantly greater effect on glycerol release compared with WT but similar effect on cholesterol efflux. Pharmacological inhibition or siRNA silencing of ABCA-1 did not diminish Milano-stimulated lipolysis, although binding to the cell surface was decreased, as analyzed by fluorescence microscopy. Interestingly, methyl-β-cyclodextrin, a well-described cholesterol acceptor, dose-dependently stimulated lipolysis. Together, these results suggest that decreased fat mass and increased lipolysis following Milano treatment in vivo is partly explained by a novel mechanism at the adipose cell level comprising stimulation of lipolysis independently of the canonical cAMP/PKA signaling pathway.
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40.
  • Liu, Li, et al. (författare)
  • Cell Type Dependent Suppression of Inflammatory Mediators by Myocardin Related Transcription Factors
  • 2021
  • Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Myocardin related transcription factors (MRTFs: MYOCD/myocardin, MRTF-A, and MRTF-B) play a key role in smooth muscle cell differentiation by activating contractile genes. In atherosclerosis, MRTF levels change, and most notable is a fall of MYOCD. Previous work described anti-inflammatory properties of MRTF-A and MYOCD, occurring through RelA binding, suggesting that MYOCD reduction could contribute to vascular inflammation. Recent studies have muddled this picture showing that MRTFs may show both anti- and pro-inflammatory properties, but the basis of these discrepancies remain unclear. Moreover, the impact of MRTFs on inflammatory signaling pathways in tissues relevant to human arterial disease is uncertain. The current work aimed to address these issues. RNA-sequencing after forced expression of myocardin in human coronary artery smooth muscle cells (hCASMCs) showed reduction of pro-inflammatory transcripts, including CCL2, CXCL8, IL6, and IL1B. Side-by-side comparison of MYOCD, MRTF-A, and MRTF-B in hCASMCs, showed that the anti-inflammatory impact was shared among MRTFs. Correlation analyses using human arterial transcriptomic datasets revealed negative correlations between MYOCD, MRTFA, and SRF, on the one hand, and the inflammatory transcripts, on the other. A pro-inflammatory drive from lipopolysaccharide, did not change the size of the suppressive effect of MRTF-A in hCASMCs on either mRNA or protein levels. To examine cell type-dependence, we compared the anti-inflammatory impact in hCASMCs, with that in human bladder SMCs, in endothelial cells, and in monocytes (THP-1 cells). Surprisingly, little anti-inflammatory activity was seen in endothelial cells and monocytes, and in bladder SMCs, MRTF-A was pro-inflammatory. CXCL8, IL6, and IL1B were increased by the MRTF-SRF inhibitor CCG-1423 and by MRTF-A silencing in hCASMCs, but depolymerization of actin, known to inhibit MRTF activity, had no stimulatory effect, an exception being IL1B. Co-immunoprecipitation supported binding of MRTF-A to RelA, supporting sequestration of this important pro-inflammatory mediator as a mechanism. Dexamethasone treatment and silencing of RelA (by 76 ± 1%) however only eliminated a fraction of the MRTF-A effect (≈25%), suggesting mechanisms beyond RelA binding. Indeed, SRF silencing suggested that MRTF-A suppression of IL1B and CXCL8 depends on SRF. This work thus supports an anti-inflammatory impact of MRTF-SRF signaling in hCASMCs and in intact human arteries, but not in several other cell types.
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41.
  • Liu, Li, et al. (författare)
  • Myocardin regulates exon usage in smooth muscle cells through induction of splicing regulatory factors
  • 2022
  • Ingår i: Cellular and Molecular Life Sciences. - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 79:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Differentiation of smooth muscle cells (SMCs) depends on serum response factor (SRF) and its co-activator myocardin (MYOCD). The role of MYOCD for the SMC program of gene transcription is well established. In contrast, the role of MYOCD in control of SMC-specific alternative exon usage, including exon splicing, has not been explored. In the current work we identified four splicing factors (MBNL1, RBPMS, RBPMS2, and RBFOX2) that correlate with MYOCD across human SMC tissues. Forced expression of MYOCD family members in human coronary artery SMCs in vitro upregulated expression of these splicing factors. For global profiling of transcript diversity, we performed RNA-sequencing after MYOCD transduction. We analyzed alternative transcripts with three different methods. Exon-based analysis identified 1637 features with differential exon usage. For example, usage of 3´ exons in MYLK that encode telokin increased relative to 5´ exons, as did the 17 kDa telokin to 130 kDa MYLK protein ratio. Dedicated event-based analysis identified 239 MYOCD-driven splicing events. Events involving MBNL1, MCAM, and ACTN1 were among the most prominent, and this was confirmed using variant-specific PCR analyses. In support of a role for RBPMS and RBFOX2 in MYOCD-driven splicing we found enrichment of their binding motifs around differentially spliced exons. Moreover, knockdown of either RBPMS or RBFOX2 antagonized splicing events stimulated by MYOCD, including those involving ACTN1, VCL, and MBNL1. Supporting an in vivo role of MYOCD-SRF-driven splicing, we demonstrate altered Rbpms expression and splicing in inducible and SMC-specific Srf knockout mice. We conclude that MYOCD-SRF, in part via RBPMS and RBFOX2, induce a program of differential exon usage and alternative splicing as part of the broader program of SMC differentiation.
  •  
42.
  • Lizunov, Vladimir A, et al. (författare)
  • Human adipose cells in vitro are either refractory or responsive to insulin, reflecting host metabolic state.
  • 2015
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:3
  • Tidskriftsartikel (refereegranskat)abstract
    • While intercellular communication processes are frequently characterized by switch-like transitions, the endocrine system, including the adipose tissue response to insulin, has been characterized by graded responses. Yet here individual cells from adipose tissue biopsies are best described by a switch-like transition between the basal and insulin-stimulated states for the trafficking of the glucose transporter GLUT4. Two statistically-defined populations best describe the observed cellular heterogeneity, representing the fractions of refractive and responsive adipose cells. Furthermore, subjects exhibiting high systemic insulin sensitivity indices (SI) have high fractions of responsive adipose cells in vitro, while subjects exhibiting decreasing SI have increasing fractions of refractory cells in vitro. Thus, a two-component model best describes the relationship between cellular refractory fraction and subject SI. Since isolated cells exhibit these different response characteristics in the presence of constant culture conditions and milieu, we suggest that a physiological switching mechanism at the adipose cellular level ultimately drives systemic SI.
  •  
43.
  • Lizunov, Vladimir A., et al. (författare)
  • Impaired Tethering and Fusion of GLUT4 Vesicles in Insulin-Resistant Human Adipose Cells
  • 2013
  • Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 62:9, s. 3114-3119
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic glucose homeostasis is profoundly influenced by adipose cell function. Here we investigated GLUT4 dynamics in living adipose cells from human subjects with varying BMI and insulin sensitivity index (S-i) values. Cells were transfected with hemagglutinin (HA)-GLUT4-green fluorescent protein (GFP)/mCherry (red fluorescence), and were imaged live using total internal reflection fluorescence and confocal microscopy. HA-GLUT4-GFP redistribution to the plasma membrane (PM) was quantified by surface-exposed HA epitope. In the basal state, GLUT4 storage vesicle (GSV) trafficking to and fusion with the PM were invariant with donor subject S-i, as was total cell-surface GLUT4. In cells from insulin-sensitive subjects, insulin augmented GSV tethering and fusion approximately threefold, resulting in a corresponding increase in total PM GLUT4. However, with decreasing S-i, these effects diminished progressively. All insulin-induced effects on GLUT4 redistribution and trafficking correlated strongly with S-i and only weakly with BMI. Thus, while basal GLUT4 dynamics and total cell-surface GLUT4 are intact in human adipose cells, independent of donor S-i, cells from insulin-resistant donors show markedly impaired GSV tethering and fusion responses to insulin, even after overnight culture. This altered insulin responsiveness is consistent with the hypothesis that adipose cellular dysfunction is a primary contributor to systemic metabolic dysfunction.
  •  
44.
  • Lizunov, Vladimir A., et al. (författare)
  • Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice
  • 2012
  • Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 302:8, s. 950-960
  • Tidskriftsartikel (refereegranskat)abstract
    • Insulin stimulates fusion, but not tethering, of GLUT4 vesicles in skeletal muscle of HA-GLUT4-GFP transgenic mice. Am J Physiol Endocrinol Metab 302: E950-E960, 2012. First published January 31, 2012; doi:10.1152/ajpendo.00466.2011.-Insulin regulates glucose uptake into fat and muscle by modulating the subcellular distribution of GLUT4 between the cell surface and intracellular compartments. However, quantification of these translocation processes in muscle by classical subcellular fractionation techniques is confounded by contaminating microfibrillar protein; dynamic studies at the molecular level are almost impossible. In this study, we introduce a muscle-specific transgenic mouse model in which HA-GLUT4-GFP is expressed under the control of the MCK promoter. HA-GLUT4-GFP was found to translocate to the plasma membrane and T-tubules after insulin stimulation, thus mimicking endogenous GLUT4. To investigate the dynamics of GLUT4 trafficking in skeletal muscle, we quantified vesicles containing HA-GLUT4-GFP near the sarcolemma and T-tubules and analyzed insulin-stimulated exocytosis at the single vesicle level by total internal reflection fluorescence and confocal microscopy. We found that only 10% of the intracellular GLUT4 pool comprised mobile vesicles, whereas most of the GLUT4 structures remained stationary or tethered at the sarcolemma or T-tubules. In fact, most of the insulin-stimulated exocytosis emanated from pretethered vesicles, whereas the small pool of mobile GLUT4 vesicles was not significantly affected by insulin. Our data strongly suggest that the mobile pool of GLUT4 vesicles is not a major site of insulin action but rather locally distributed. Most likely, pretethered GLUT4 structures are responsible for the initial phase of insulin-stimulated exocytosis.
  •  
45.
  • Malm, Joakim, et al. (författare)
  • UTVÄRDERING AV SI-VERKSAMHETEN VID LUNDS UNIVERSITET 2019/20
  • 2020
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Enkelt uttryckt är Samverkansinlärning (SI) en studiecirkel kopplat till en utmanande kurs. SI leds av en senior student som utformar läraktiviteter där studenterna arbetar i grupper med att förklara och förtydliga svårt kursmaterial. Målsättningen med SI, förutom förbättrade prestationer i den aktuella kursen, är att studenterna skall utveckla goda studiestrategier och bli mer självständiga i sitt lärande. Denna rapport behandlar SI-verksamheten vid Lunds universitet under läsåret 2019/20. Målsättningen är att läsaren skall få en god bild av hur SI bedrivs vid lärosätet och hur insatsen upplevs av deltagare och studentledare. Rapporten bygger dels på kvantitativa data – SI-närvaro samt närvaron kopplat till studenternas prestationer i SI-stödda kurser. Och dels på kvalitativa data från enkäter till deltagare och SI-ledare samt information frän metodhandledare och SI-koordinatorer.Under läsåret 2019/20 kompletterades undervisningen i 160 kurstillfällen av SI där totalt 235 studentledare ledde SI-pass. 4200 studenter vid universitetet deltog på passen under läsåret. Medelnärvaron var 25 % och 50 % av studenter med tillgång till SI provade på att besöka åtminstone ett pass. Dessa siffror betyder att SI-verksamheten vid Lunds universitet är en av de största vid lärosäten i Europa. SI-verksamheten följer också grundläggande SI-principer på ett bra sätt enligt deltagarna. Exempelvis på så sätt att deltagarna har ett stort inflytande över agendan på SI-passen och att arbetet med att förstå utmanande kursmaterial bedrivs genom arbete och diskussion i grupp. SI-ledaren ser till att arbetet går framåt genom att ställa frågor och uppmuntrardeltagarna att dela med sig av sina kunskaper till varandra. Studenternas drivkraft att gå på SI-passen är i huvudsak meningsorienterad genom att de vill få en bättre förståelse av ämnet och för att det är roligt att diskutera kursinnehåll med kurskamrater. Vad ger då deltagande på SI för närvarande studenter? Jämförelser av närvaro på SI och genomströmning på SI-stödd kurs antyder att chanserna att klara kursen vid ordinarie examination(er) ökar med ökad SI-närvaro. Deltagande studenter upplever dessutom i stor utsträckning att SI leder till att de bättre förstår vad som förväntas av dem i kursen, är ett effektivt stöd att ta sig fram i kursen, ökar intresset för ämnet och ger dem en djupare förståelse av kursinnehållet. Dessutom anser en stor andel avdeltagarna att de utvecklar generella färdigheter såsom problemlösning, kritiskt tänkande, lagarbete och presentation av akademiskt material inför andra. En betydande del av SI-deltagarna anger att de åtminstone till viss del de utvecklar sitt sätt att studera och förbättrar sitt akademiska självförtroende. Ca en fjärdedel av de svarande på enkäten anser att SI varit viktigt för att skaffa studiekamrater, vilket kan vara mycket betydelsefullt för att känna tillhörighet inom akademien och ge ytterligare motivation till fortsatta högre studier.De dominerande svarsteman på öppna enkätfrågor rörande vad som är bäst med SI samt vad som skiljer SI-pass från ordinarie undervisning är desamma för bägge frågorna. Det handlar om att deltagarna uppskattar diskussionen/samarbetet samt atmosfären och arbetsmiljön på passen. Vidare gillar studenterna fokus på djupare förståelse av kursinnehållet. På frågan vad man tycker kan förbättras med SI-passen anser en del av deltagarna att strukturen på passet ibland kan vara tydligare och att arbetet under passen ibland kan kännas ineffektivt.Aktiva SI-ledare och SI-ledaralumner i arbetslivet fick svara på enkäter rörande de färdigheter man tränar och utvecklar i sitt SI-arbete. Här framkom att de svarande generellt tyckte att de blivit bättre på ett flertal färdigheter inom områdena kommunikation, ledarskap och handhavande av grupper samt vissa personliga färdigheter. En stor majoritet av SI-ledaralumnerna ansåg dessutom SI-ledarskapet givit dem en fördel när de sökt jobb och att man haft god nytta av SI-färdigheterna i sitt yrkesverksamma liv. Enkätundersökningen avaktiva SI-ledare samt SI-ledaralumner vid Lunds Universitet var en del av en internationell undersökning där två andra SI-program vid North West University i Sydafrika och University of Missouri Kansas City ingick. Resultaten från enkäterna vid dessa lärosäten speglade resultaten från Lunds universitet. Således verkar SI-ledarna generellt vinna en hel del genom sin tjänstgöring, oavsett lärosäte och land, som de senare har nytta av i sitt yrkesverksamma liv.Under den andra hälften av vårterminen 2020 övergick SI-passen till att ges på distans pga Coronapandemin. Många metodhandledare och SI-ledare gjorde ett fantastiskt jobb med att snabbt ställa om verksamheten. Enkätsvar från deltagare på distans-SI visade att SI-passen var uppskattade och att fördelarna man fick från att delta motsvarade de som man får på reguljär sals-SI. Dock framträdde ett antal utmaningar. Närvaron var betydligt lägre på distans-SI jämfört med sals-SI. Mötena kändes ofta som lite mer tidsineffektiva när de gickpå distans, ledarna fick en svårare uppgift med att hålla reda på tekniken vid sidan av att leda SI-passet, och deltagarna/ledarna saknade den sociala dimensionen man får vid sals-SI med möjlighet att kunna snacka liteom annat och att kunna läsa av kroppsspråk. Möjligheten att prova på distans-SI vid Lunds universitet har varit berikande och gett inspiration till att utveckla konceptet. Distans SI bör även i mer normala tider kunna vara ett bra komplement till sals-SI vad gäller att stödja studenter i utmanande kurser. Speciellt vid distanskurser, men även för att stödja studenter som inte har möjlighet att delta på sals-SI, exempelvis pga föräldraskap, deltidsarbete, långa pendlingstider, mm mm.Under läsåret 2019/20 gjordes också en studie av läraktiviteter under SI-pass. Studien visade att de huvudsakliga aktiviteterna på SI-pass handlar om att förklara och tydliggöra det som är svårt i kursen. Men att man också avsätter betydande del av tiden för att få en djupare förståelse av det behandlade kursmaterialet genom analyserande och reflekterande aktiviteter.
  •  
46.
  • Malm, Joakim, et al. (författare)
  • Utvärdering av SI-verksamheten vid Lunds universitet 2022/23
  • 2023
  • Rapport (övrigt vetenskapligt/konstnärligt)abstract
    • Enkelt uttryckt är Samverkansinlärning (SI) en studiecirkel kopplat till en utmanande kurs. SI leds av en senior student som utformar läraktiviteter där studenterna arbetar i grupper med att förklara och förtydliga svårt kursmaterial. Målsättningen med SI, förutom förbättrade prestationer i den aktuella kursen, är att studenterna skall utveckla goda studiestrategier och bli mer självständiga i sitt lärande. Denna rapport behandlar SI-verksamheten vid Lunds universitet under läsåret 2022/23. Målsättningen är att läsaren skall få en god bild av hur SI bedrivs vid lärosätet och hur insatsen upplevs av deltagare och studentledare. Rapporten bygger dels på kvantitativa data – SI-närvaro, samt närvaron kopplat till studenternas prestationer i SI-stödda kurser. Och dels på kvalitativa data från enkäter till deltagare och SI-ledare, dels information frän metodhandledare och SI-koordinatorer. Under läsåret 2022/23 kompletterades undervisningen i 204 kurstillfällen av SI där totalt 266 studentledare ledde SI-pass. 5200 studenter vid universitetet deltog på passen under läsåret. Medelnärvaron var 23 % och 53% av studenter med tillgång till SI provade på att besöka åtminstone ett pass. Dessa siffror betyder att SI-verksamheten vid Lunds universitet är en av de största vid lärosäten i Europa (SI finns på 75+ högre lärosäten i Europa). SI-verksamheten följer också grundläggande SI-principer på ett bra sätt enligt deltagarna. Exempelvis på så sätt att deltagarna har ett stort inflytande över agendan på SI-passen och att arbetet med att förstå utmanande kursmaterial bedrivs genom arbete och diskussion i grupp. SI-ledaren ser till att arbetet gårframåt genom att ställa frågor och uppmuntrar deltagarna att dela med sig av sina kunskaper till varandra.Studenternas drivkraft att gå på SI-passen är i huvudsak meningsorienterad genom att de vill få en bättre förståelse av ämnet och för att det är roligt att diskutera kursinnehåll med kurskamrater. Vad ger då deltagande på SI för närvarande studenter? Jämförelser av närvaro på SI och genomströmning på SI-stödd kurs antyder att chanserna att klara kursen vid ordinarie examination(er) ökar med ökad SI-närvaro. Deltagande studenter upplever dessutom i stor utsträckning att SI leder till att de bättre förstår vad som förväntas av dem i kursen, är ett effektivt stöd att ta sig fram i kursen, ökar intresset för ämnet och ger dem en djupare förståelse av kursinnehållet. Dessutom anser en stor andel av deltagarna att de utvecklar generella färdigheter såsom problemlösning, kritiskt tänkande, lagarbete och presentation av akademiskt material införandra. En betydande del av SI-deltagarna anger att de åtminstone till viss del utvecklar sitt sätt att studera och förbättrar sitt akademiska självförtroende. Lite mer än en fjärdedel av de svarande på enkäten anser att SI varit viktigt för att skaffa studiekamrater, vilket kan vara mycket betydelsefullt för att känna tillhörighet inom akademien och ge ytterligare motivation till fortsatta högre studier.De dominerande svarsteman på öppna enkätfrågor rörande vad som är bäst med SI samt vad som skiljer SI-pass från ordinarie undervisning är desamma för bägge frågorna. Det handlar om att deltagarna uppskattar diskussionen/samarbetet samt atmosfären och arbetsmiljön på passen. Vidare gillar studenterna fokus på djupare förståelse av kursinnehållet. På frågan vad man tycker kan förbättras med SI-passen anser en del av deltagarna att strukturen på passet ibland kan vara tydligare och att arbetet under passen ibland kan kännas ineffektivt.Det är roligt att konstatera att de allra flesta SI-ledarna trivs i sin roll, känner sig nöjda med sitt jobb och upplever att de gör skillnad för sina deltagare, baserat på deras enkätsvar. Dessutom utvecklar de i hög grad i olika färdigheter som kommunikation, grupphantering och ledarskap.
  •  
47.
  • Marcondes, Rodrigo R., et al. (författare)
  • Exercise differentially affects metabolic functions and white adipose tissue in female letrozole-and dihydrotestosterone-induced mouse models of polycystic ovary syndrome
  • 2017
  • Ingår i: Molecular and Cellular Endocrinology. - : Elsevier. - 0303-7207 .- 1872-8057. ; 448, s. 66-76
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. 
  •  
48.
  • Minniti, Maria, et al. (författare)
  • Boyan Jovanovic : recipient of the 2019 Global Award for Entrepreneurship Research
  • 2019
  • Ingår i: Small Business Economics. - : SPRINGER. - 0921-898X .- 1573-0913. ; 53:3, s. 547-553
  • Tidskriftsartikel (refereegranskat)abstract
    • The 2019 Global Award for Entrepreneurship Research has been awarded to Professor Boyan Jovanovic at New York University in the USA. Boyan Jovanovic has developed pioneering research that advances our understanding of the competitive dynamics between incumbent firms and new entrants, entrepreneurial learning and selection processes, and the importance of entrepreneurship for the economy. Key perspectives in his research are that the entrepreneur makes employment choices based on the comparative advantage of his or her skills and that entrepreneurial firms are vehicles of technological change and knowledge diffusion that influence industry dynamics and, in turn, economic growth.
  •  
49.
  •  
50.
  • Morén, Björn, et al. (författare)
  • EHD2 regulates adipocyte function and is enriched at cell surface-associated lipid droplets in primary human adipocytes
  • 2019
  • Ingår i: Molecular Biology of the Cell. - : AMER SOC CELL BIOLOGY. - 1059-1524 .- 1939-4586. ; 30:10, s. 1147-1159
  • Tidskriftsartikel (refereegranskat)abstract
    • Adipocytes play a central role in energy balance, and dysfunctional adipose tissue severely affects systemic energy homeostasis. The ATPase EH domain-containing 2 (EHD2) has previously been shown to regulate caveolae, plasma membrane-specific domains that are involved in lipid uptake and signal transduction. Here, we investigated the role of EHD2 in adipocyte function. We demonstrate that EHD2 protein expression is highly up-regulated at the onset of triglyceride accumulation during adipocyte differentiation. Small interfering RNA-mediated EHD2 silencing affected the differentiation process and impaired insulin sensitivity, lipid storage capacity, and lipolysis. Fluorescence imaging revealed localization of EHD2 to caveolae, close to cell surface-associated lipid droplets in primary human adipocytes. These lipid droplets stained positive for glycerol transporter aquaporin 7 and phosphorylated perilipin-1 following adrenergic stimulation. Further, EHD2 overexpression in human adipocytes increased the lipolytic signaling and suppressed the activity of transcription factor PPAR.. Overall, these data suggest that EHD2 plays a key role for adipocyte function.
  •  
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