| 1. |
- Bäck, Karolina, 1981-
(author)
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Interaction between insulin and IGF-I receptors in insulin sensitive and insulin resistant cells and tissues
- 2011
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Doctoral thesis (other academic/artistic)abstract
- Insulin and insulin-like growth factor I (IGF-I) are two related peptides with similar structure. They mediate their effects by binding to their respective receptor, the insulin receptor (IR) and the IGF-I receptor (IGF-IR) and induce intracellular signalling cascades resulting in metabolic or mitogenic effects. The relative abundance of IR and IGF-IR is of importance for the type of effect that is the outcome of the signal. There are few studies investigating the relative receptor abundance and its effects in human cells and tissues.In this thesis we wanted to study abundance and regulation of insulin and IGF-I receptors in different human cells and tissues and examine the effects of variations in insulin and IGF-I receptor abundance between different cells and tissues.We examined IR and IGF-IR gene and protein expression and the effects of insulin and IGF-I on receptor phosphorylation, DNA synthesis and glucose transport.Our results show that there is a large variation in the distribution of IR and IGF-IR in different human cells and tissues. Renal artery intima-media expressed predominantly IGF-IR while in liver IR was the predominant receptor type.Differentiation of human preadipocytes results in a change in relative expression of IGF-IR to IR. Mature adipocytes express almost 10-fold more IR than IGF-IR while preadipocytes express almost the same amounts of both receptors. Mature tissues, such as liver, skeletal muscle, myometrium and renal artery intima-media, express predominantly IR-B. Preadipocytes express IR-A and the expression of IR-B is induced during differentiation.We could show the presence of insulin/IGF-I hybrid receptors in preadipocytes but not in mature adipocytes. Cultured endothelial cells express mostly IGF-IR and insulin/IGF-I hybrid receptors and these cells respond mainly to IGF-I. Due to the large abundance of IR mature adipocytes are sensitive to insulin but insensitive to IGF-I whereas preadipocytes expressing equal amounts of both receptors respond to both insulin and IGF-I. Insulin and IGF-I are only partial agonists to each other’s receptors in human preadipocytes and adipocytes.The overall results indicate that differential expression of IGF-IR and IR is a key mechanism in regulation of growth and metabolism.
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| 2. |
- Ahlzén, Maja, et al.
(author)
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Expression of the transcription factor 7-like 2 gene (TCF7L2) in human adipocytes is down regulated by insulin.
- 2008
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In: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 370, s. 49-52
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Journal article (peer-reviewed)abstract
- Variants in the TCF7L2 gene (transcription factor 7-like 2) have shown strong association with type 2 diabetes with two defined risk haplotypes, HapA and HapB(T2D). TCF7L2 may play a role in both glucose homeostasis and adipogenesis. Our aim was to characterize the TCF7L2 mRNA expression and regulation in human adipose tissue. We quantified TCF7L2 mRNA levels in cultured human adipocytes and in biopsies from visceral (VAT) and subcutaneous (SAT) adipose tissue from 38 obese non-diabetic subjects, using real-time PCR. The influence of haplotype and clinical traits on TCF7L2 mRNA levels were investigated. In vitro, insulin decreased TCF7L2 mRNA expression. This effect was attenuated in cells incubated with the free fatty acids palmitate or oleate. In vivo, we found significantly higher expression in SAT from more insulin resistant subjects. No correlations between TCF7L2 mRNA expression and obesity measures were observed. TCF7L2 expression was higher in VAT than in SAT and when stratifying for haplotype, this difference was seen in HapA carriers but not in non-HapA carriers. In conclusion, TCF7L2 mRNA levels in adipocytes are decreased by insulin and seem to increase in insulin resistant subjects and in HapA carriers.
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| 3. |
- Belfrage, Per, et al.
(author)
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Alterations of lipid metabolism in healthy volunteers during long-term ethanol intake
- 1977
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In: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 7:2, s. 127-131
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Journal article (peer-reviewed)abstract
- Nine young, healthy male volunteers were given ethanol (75 g/day) for 5 weeks. The ethanol was divided into five daily doses and taken so that blood ethanol levels never exceeded 0.04% (w/v). During the latter part of the ethanol intake period, there was a significant, transient increase of plasma triglyceride (TG) concentrations followed by reduction to normal levels. A three-fold increase of lipoprotein lipase activity (LLA) occurred in biopsy specimens of adipose tissue. An increase of alpha-lipoprotein concentrations, which correlated significantly with the decrease in plasma TG levels and the increase in adipose LLA, was also observed during the ethanol intake period. No changes were observed in plasma cholesterol and beta-lipoprotein levels. A transient, three-fold increase of TG concentrations occurred in liver biopsy specimens. Ultrastructural and cytochemical examinations of the biopsy specimens showed hyperplasia of the smooth endoplasmic reticulum, and increased canallicular activity of gamma-glutamyl transferase (gamma-GT) activity in most subjects towards the end of and after the ethanol intake period. Serum gamma-GT levels also increased significantly.
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| 4. |
- Bickerton, A. S. T., et al.
(author)
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Adipose tissue fatty acid metabolism in insulin-resistant men
- 2008
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 51:8, s. 1466-1474
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Journal article (peer-reviewed)abstract
- Aims/hypothesis Increased NEFA production and concentrations may underlie insulin resistance. We examined systemic and adipose tissue NEFA metabolism in insulin-resistant overweight men (BM1 25-35 kg/m(2)). Methods In a cohort study we examined NEFA concentrations in men in the upper quartile of fasting insulin (n = 124) and in men with fasting insulin below the median (n 159). In a metabolic study we examined NEFA metabolism in the fasting and postprandial states, in ten insulin-resistant men and ten controls. Results In the cohort study, fasting NEFA concentrations were not significantly different between the two groups (median values: insulin-resistant men, 410 mu mol/l; controls, 445 2 mu mol/l). However, triacylglycerol concentrations differed markedly (1.84 vs 1.18 mmol/l respectively, p<0.001). In the metabolic study, arterial NEFA concentrations again did not differ between groups, whereas triacylglycerol concentrations were significantly higher in insulin-resistant men. Systemic NEFA production and the release of NEFA from subcutaneous adipose tissue, expressed per unit of fat mass, were both reduced in insulin-resistant men compared with controls (fasting values by 32%, p=0.02, and 44%, p=0.04 respectively). 3-Hydroxybutyrate concentrations, an index of hepatic fat oxidation and ketogenesis, were lower (p=0.03). Conclusions/interpretation Adipose tissue NEFA output is not increased (per unit weight of tissue) in insulin resistance. On the contrary, it appears to be suppressed by high fasting insulin concentrations. Alterations in triacylglycerol metabolism are more marked than those in NEFA metabolism. and are indicative of altered metabolic partitioning of fatty acids (decreased oxidation, increased esterification) in the liver.
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| 5. |
- Bott, Lukas Thomas, et al.
(author)
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Coulomb dissociation of O-16 into He-4 and C-12
- 2023
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In: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
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Conference paper (peer-reviewed)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
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| 6. |
- Fischer-Posovszky, Pamela, et al.
(author)
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Human SGBS Cells - a Unique Tool for Studies of Human Fat Cell Biology
- 2008
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In: Obesity Facts. - : S. Karger AG. - 1662-4033 .- 1662-4025. ; 1:4, s. 184-189
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Research review (peer-reviewed)abstract
- The human Simpson-Golabi-Behmel syndrome (SGBS) preadipocyte cell strain provides a unique and useful tool for studies of human adipocyte biology. The cells originate from an adipose tissue specimen of a patient with SGBS. They are neither transformed nor immortalized, and provide an almost unlimited source due to their ability to proliferate for up to 50 generations with retained capacity for adipogenic differentiation. So far, the cells have been used for a number of studies on adipose differentiation, adipocyte glucose uptake, lipolysis, apoptosis, regulation of expression of adipokines, and protein translocation. The cells are efficiently differentiated in the presence of PPAR gamma agonists and in the absence of serum and albumin. SGBS adipocytes respond to insulin stimulation by increasing glucose uptake several-fold (EC50 approximately 100 pmol/l), and by very effectively inhibiting (IC50 approximately 10 pmol/l) catecholamine-stimulated lipolysis.
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| 7. |
- Heijl, Anders, et al.
(author)
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Nordic research in ophthalmology.
- 2005
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In: Acta ophthalmologica Scandinavica. - : Wiley. - 1395-3907 .- 1600-0420. ; 83:3, s. 278-88
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Journal article (other academic/artistic)abstract
- Nordic ophthalmologists and vision scientists are active in many fields of eye research. This is most evident at the biannual Nordic Congress of Ophthalmology, most recently held in Malmö in June 2004. The authors here review some of the research in vision and ophthalmology presented at this meeting or published recently by Nordic scientists. This paper does not represent a comprehensive review of all Nordic research in the field, but attempts to give an overview of some of the activities underway in eye research in this part of the world.
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| 8. |
- Johansson, Lovisa, et al.
(author)
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Variation in the adiponutrin gene influences its expression and associates with obesity.
- 2006
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 55:3, s. 826-833
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Journal article (peer-reviewed)abstract
- Adiponutrin is one of three recently identified adipocyte lipases. Surprisingly, these proteins also retain transacylase activity, a hitherto unknown pathway of triacylglycerol synthesis in the adipocytes. This may enable them to participate in both anabolic and catabolic processes. The adiponutrin gene (ADPN) is downregulated by fasting and upregulated by refeeding, suggesting a role in lipogenesis. Experiments in human adipocytes confirmed that the gene is upregulated in response to insulin in a glucose-dependent fashion. Obese subjects had increased levels of subcutaneous and visceral abdominal adipose tissue ADPN mRNA. Visceral ADPN mRNA expression was correlated to measures of insulin sensitivity (fasting insulin and homeostasis model assessment). We also studied genetic variation in ADPN and its relation to obesity, lipolysis, and mRNA expression. Two ADPN polymorphisms showed association with obesity. Carriers of the obesity-associated variants showed a lesser increase in the levels of adipose tissue ADPN mRNA and an increased basal lipolysis. Our results suggest that obese subjects that are insulin resistant and/or carriers of the obesity-associated ADPN alleles fail to upregulate the gene and that upregulation of adiponutrin may be an appropriate response to orchestrate energy excess.
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| 9. |
- Lagerqvist, Bosse, 1957, et al.
(author)
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Natur- och kulturmiljöer vid vatten – samverkan för framgång. Rapport från ett pilotprojekt
- 2022
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Book (other academic/artistic)abstract
- Rapporten beskriver resultatet av ett pilotprojekt som har genomförts 2021–22, med syfte att beskriva exempel på en positiv samverkan mellan natur- och kulturmiljövården i samband med åtgärder vidtagna utifrån Vattenförvaltningsförordningen och där vattenanknutna kulturmiljöer berörs. Projektet har finansierats genom anslag från Riksantikvarieämbetet, och har genomförts av Västra Götalandsregionen (Förvaltningen för kulturutveckling), Göteborgs universitet (Institutionen för kulturvård) och Vattenhistoriskt Nätverk/Arbetets museum. Bakgrunden är EU:s Vattendirektiv som har som syfte att stoppa försämringen av vattenförekomster och nå ”god status” för Europas floder, sjöar och grundvatten. I de fall där kulturmiljöer med lång historia, t.ex. kvarnanläggningar och flottningsleder, är placerade i eller i direkt anslutning till strömmande vatten, har de ofta betraktats som hinder för att uppnå god ekologisk status. Utrivning av dammanläggningar är därför den enkla lösningen, alternativt att omlöp görs utan att först ha konstaterat den eventuella förekomsten av arkeologiska lämningar i omlöpets väg. Kulturmiljövården som en sakägare är ofta satt på undantag och saknar också särskild finansiering för att kunna prioritera åtgärder i vattenanknutna kulturmiljöer. En ytterligare bakgrund till projektet är den Nationella planen för omprövning av vattenkraften (NAP) som på likartat sätt kan innebära utrivning av dammanläggningar. Vad gäller kulturmiljövården är det enkelt att konstatera att den inte kan delta på jämbördigt sätt som naturvårdens och ekologins företrädare, p.g.a. avsaknad av finansiering. Samtidigt har kulturmiljövården en formell roll att tillse att Kulturmiljölagens skrivningar om fornlämningar och fornfynd efterlevs – vare sig det gäller utrivning av vattenplacerade konstruktioner eller anläggande av omlöp. Det är därför nödvändigt att finansieringen av kulturmiljövårdens deltagande förstärks. Projektet föreslår att för projekt kring åtgärder för ekologisk status som omfattar kulturhistoriska miljöer, borde länsstyrelserna kunna samordna berörda enheter i ett gemensamt projektansvar för att tillförsäkra att berörda regelverk efterlevs. Vattenförvaltningsförordningen är den grundläggande författningen, men i många processer berörs också Miljöbalken, Kulturmiljölagen, Plan- och bygglagen, och projektet förslår att en funktion i linje med Boverkets PBL Kunskapsbanken, etableras för frågor som rör vattenanknutna kulturmiljöer. När det gäller att skapa välfungerande grupperingar kring åtgärder som föranleds av vattendirektivet eller NAP, så kan Vattenråden vara potentiella arenor med formella kontakter med berörda länsstyrelser.
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| 10. |
- Newell, Felicity S., et al.
(author)
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Characterization of the transcriptional and functional effects of fibroblast growth factor-1 on human preadipocyte differentiation
- 2006
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In: FASEB Journal. - : Wiley. - 1530-6860 .- 0892-6638. ; 20:14, s. 2615-2615
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Journal article (peer-reviewed)abstract
- We recently established that fibroblast growth factor (FGF)-1 promotes adipogenesis of primary human preadipocytes (phPA). In the current report, we have characterized the adipogenic effects of FGF-1 in phPA and also in a human PA strain derived from an individual with Simpson-Golabi-Behmel syndrome (SGBS PA), which exhibit an intrinsic capacity to differentiate with high efficiency. In further studies, we compared these models with the well-characterized murine 3T3-L1 preadipocyte cell line (3T3-L1 PA). FGF-1 up-regulated the adipogenic program in phPA, with increased expression of peroxisome proliferator-activated receptor-gamma in confluent PA prior to induction of differentiation and increased expression of adipocyte markers during differentiation. Moreover, phPA differentiated in the presence of FGF-1 were more insulin responsive and secreted increased levels of adiponectin. FGF-1 treatment of SGBS PA further enhanced differentiation. For the most part, the adipogenic program in phPA paralleled that observed in 3T3-L1 PA; however, we found no evidence of mitotic clonal expansion in the phPA. Finally, we investigated a role for extracellular regulated kinase 1/2 (ERK 1/2) in adipogenesis of phPA. FGF-1 induced robust phosphorylation of ERK1/2 in early differentiation and inhibition of ERK1/2 activity significantly reduced phPA differentiation. These data suggest that FGF-1 treated phPA represent a valuable in vitro model for the study of adipogenesis and insulin action and indicate that ERK1/2 activation is necessary for human adipogenesis in the absence of mitotic clonal expansion.
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