| 1. |
- Drott, Carl Johan, et al.
(författare)
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Ghrelin in rat pancreatic islets decreases islet blood flow
- 2019
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 317:1, s. E139-E146
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Tidskriftsartikel (refereegranskat)abstract
- The peptide ghrelin is mainly produced in some of the epithelial cells in the stomach, but also, during starvation, by the epsilon-cells in the endocrine pancreas. Ghrelin, as an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1 alpha). exerts a variety of metabolic functions including stimulation of appetite and weight gain. Its complete role is not yet fully understood, including whether it has any vascular functions. The present study evaluated if ghrelin affects pancreatic and islet blood flow. Ghrelin and the GHS-R1 alpha receptor antagonist GHRP-6 were injected intravenously in rats followed by blood flow measurements using a microsphere technique. Ghrelin decreased, while GHRP-6 in fasted, but not fed, rats selectively increased islet blood flow fourfold. GHS-R1 alpha was identified not only on glucagon-producing cells but also seemed to be present in the islet arterioles. GHRP-6 in fasted rats. only, also improved the peak insulin response to glucose in vivo. thereby substantially blunting the hyperglycemia. GHRP-6 doubled glucose-stimulated insulin release in vitro of both islets obtained from fed and fasted rats. Our results indicate a novel role for endogenous ghrelin acting directly or indirectly as a local vasoconstrictor in the islets during fasting, thereby restricting the insulin response to hyperglycemia. This is to the best of our knowledge the first report that shows this physiological mechanism to restrict insulin delivery from the islets by acting on the vasculature; a mode of action that can be envisaged to complement the previously well-described mechanisms of ghrelin acting directly on the islet endocrine cells.
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| 2. |
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| 3. |
- Espes, Daniel, 1985-, et al.
(författare)
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Function and Gene Expression of Islets Experimentally Transplanted to Muscle and Omentum
- 2020
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Ingår i: Cell Transplantation. - THOUSAND OAKS, CA USA : SAGE Publications. - 0963-6897 .- 1555-3892. ; 29, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Islet transplantation to the liver is a potential curative treatment for patients with type 1 diabetes. Muscle and the greater omentum are two alternative implantation sites, which can provide excellent engraftment and hold potential as future sites for stem-cell-derived beta-cell replacement. We evaluated the functional outcome after islet transplantation to muscle and omentum and found that alloxan-diabetic animals were cured with a low number of islets (200) at both sites. The cured animals had a normal area under the curve blood glucose response to intravenous glucose, albeit animals with intramuscular islet grafts had increased 120-min blood glucose levels. They also demonstrated an exaggerated counter regulatory response to hypoglycemia. The expression of genes important for beta-cell function was, at both implantation sites, comparable to that in native pancreatic islets. The gene expression of insulin (INS1 and INS2) and glucose transporter-2 was even increased, and the expression of lactate dehydrogenase decreased, at both sites when compared to native islets. We conclude that muscle and omentum provide excellent conditions for engraftment of transplanted islets. When compared to control, 200 islets implanted to the omentum displayed a restored glucose tolerance, whereas animals with intramuscular islet grafts of similar size displayed mild glucose intolerance.
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| 4. |
- Fransén, Karin, 1973-, et al.
(författare)
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Polymorphism in the retinoic acid metabolizing enzyme CYP26B1 and the development of Crohn's disease
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:8, s. e72739-
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Tidskriftsartikel (refereegranskat)abstract
- Several studies suggest that Vitamin A may be involved in the pathogenesis of inflammatory bowel disease (IBD), but the mechanism is still unknown. Cytochrome P450 26 B1 (CYP26B1) is involved in the degradation of retinoic acid and the polymorphism rs2241057 has an elevated catabolic function of retinoic acid, why we hypothesized that the rs2241057 polymorphism may affect the risk of Crohn's disease (CD) and Ulcerative Colitis (UC). DNA from 1378 IBD patients, divided into 871 patients with CD and 507 with UC, and 1205 healthy controls collected at Örebro University Hospital and Karolinska University Hospital were analyzed for the CYP26B1 rs2241057 polymorphism with TaqMan® SNP Genotyping Assay followed by allelic discrimination analysis. A higher frequency of patients homozygous for the major (T) allele was associated with CD but not UC compared to the frequency found in healthy controls. A significant association between the major allele and non-stricturing, non-penetrating phenotype was evident for CD. However, the observed associations reached borderline significance only, after correcting for multiple testing. We suggest that homozygous carriers of the major (T) allele, relative to homozygous carriers of the minor (C) allele, of the CYP26B1 polymorphism rs2241057 may have an increased risk for the development of CD, which possibly may be due to elevated levels of retinoic acid. Our data may support the role of Vitamin A in the pathophysiology of CD, but the exact mechanisms remain to be elucidated.
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| 5. |
- Fransson, Liselotte, et al.
(författare)
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beta-cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome
- 2013
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Ingår i: Journal of Endocrinology. - : BioScientifica. - 0022-0795 .- 1479-6805. ; 219:3, s. 231-241
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids (GCs) are stress hormones primarily responsible for mobilizing glucose to the circulation. Due to this effect, insulin resistance and glucose intolerance are concerns in patients with endogenous overproduction of GCs and in patients prescribed GC-based therapy. In addition, hypercortisolemic conditions share many characteristics with the metabolic syndrome. This study reports on a thorough characterization, in terms of glucose control and lipid handling, of a mouse model where corticosterone is given via the drinking water. C57BL/6J mice were treated with corticosterone (100 or 25 mu g/ml) or vehicle in their drinking water for 5 weeks after which they were subjected to insulin or glucose tolerance tests. GC-treated mice displayed increased food intake, body weight gain, and central fat deposit accumulations. In addition, the GC treatment led to dyslipidemia as well as accumulation of ectopic fat in the liver and skeletal muscle, having a substantial negative effect on insulin sensitivity. Also glucose intolerance and hypertension, both part of the metabolic syndrome, were evident in the GC-treated mice. However, the observed effects of corticosterone were reversed after drug removal. Furthermore, this study reveals insights into beta-cell adaptation to the GC-induced insulin resistance. Increased pancreatic islet volume due to cell proliferation, increased insulin secretion capacity, and increased islet chaperone expression were found in GC-treated animals. This model mimics the human metabolic syndrome. It could be a valuable model for studying the complex mechanisms behind the development of the metabolic syndrome and type 2 diabetes, as well as the multifaceted relations between GC excess and disease.
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| 6. |
- Fransson, Liselotte, et al.
(författare)
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β-cell adaptation in a mouse model of glucocorticoid-induced metabolic syndrome
- 2013
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Ingår i: Journal of Endocrinology. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 219:3, s. 231-241
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids (GCs) are stress hormones primarily responsible for mobilizing glucose to the circulation. Due to this effect, insulin resistance and glucose intolerance are concerns in patients with endogenous overproduction of GCs and in patients prescribed GC-based therapy. In addition, hypercortisolemic conditions share many characteristics with the metabolic syndrome. This study reports on a thorough characterization, in terms of glucose control and lipid handling, of a mouse model where corticosterone is given via the drinking water. C57BL/6J mice were treated with corticosterone (100 or 25 μg/ml) or vehicle in their drinking water for 5 weeks after which they were subjected to insulin or glucose tolerance tests. GC-treated mice displayed increased food intake, body weight gain, and central fat deposit accumulations. In addition, the GC treatment led to dyslipidemia as well as accumulation of ectopic fat in the liver and skeletal muscle, having a substantial negative effect on insulin sensitivity. Also glucose intolerance and hypertension, both part of the metabolic syndrome, were evident in the GC-treated mice. However, the observed effects of corticosterone were reversed after drug removal. Furthermore, this study reveals insights into β-cell adaptation to the GC-induced insulin resistance. Increased pancreatic islet volume due to cell proliferation, increased insulin secretion capacity, and increased islet chaperone expression were found in GC-treated animals. This model mimics the human metabolic syndrome. It could be a valuable model for studying the complex mechanisms behind the development of the metabolic syndrome and type 2 diabetes, as well as the multifaceted relations between GC excess and disease.
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| 7. |
- Franzén, Markus, et al.
(författare)
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Rapid plant colonization of the forelands of a vanishing glacier is strongly associated with species traits
- 2019
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Ingår i: Arctic, Antarctic and Alpine research. - : Taylor & Francis Group. - 1523-0430 .- 1938-4246. ; 51:1, s. 366-378
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Tidskriftsartikel (refereegranskat)abstract
- Recently developed glacier forelands provide valuable insights into vegetation dynamics. We studied the vascular plants in the glacier forelands of the Almajallojekna glacier in comparison to the plants in the surrounding area. The glacier is retreating rapidly at an average rate of 0.17 km(2) per year from 1898 to 2012. In the newly emerged glacier forelands, we found that 32 percent of the 381 plant taxa occurred in the surrounding region. Sixty-eight plant species were present on the youngest terrain (0-31 y), an additional thirteen species occurred on terrain aged 32-53 years, and an additional forty-two species were detected on terrain aged 54-114 years. Of the surrounding species pool, plant species that had successfully established in recently deglaciated terrains were characterized by high regional abundance and low seed weight, and they were more likely to be members of the plant families Saxifragaceae, Salicaceae, and Asteraceae. Woody plant species with a preference for well-drained soils were more likely to be present in the youngest terrain. Our results show that the vegetation of glacier forelands is developing rapidly depending on the plant species in the surrounding area and the species' life-history traits.
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| 8. |
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| 9. |
- Franzen-Röhl, Elisabeth, et al.
(författare)
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Increased cell-mediated immune responses in patients with recurrent herpes simplex virus type 2 meningitis.
- 2011
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Ingår i: Clinical and vaccine immunology : CVI. - 1556-679X. ; 18:4, s. 655-60
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Tidskriftsartikel (refereegranskat)abstract
- The clinical picture of herpes simplex virus type 2 (HSV-2) infection includes genital blisters and less frequently meningitis, and some individuals suffer from recurrent episodes of these manifestations. We hypothesized that adaptive and/or innate immune functional deficiencies may be a major contributing factor in susceptibility to recurrent HSV-2 meningitis. Ten patients with recurrent HSV-2 meningitis were studied during clinical remission. For comparison, 10 patients with recurrent genital HSV infections as well as 21 HSV-seropositive and 19 HSV-seronegative healthy blood donors were included. HSV-specific T cell blasting and cytokine secretion were evaluated in whole blood cultures. HSV-2-induced NK cell gamma interferon production, dendritic cell Toll-like receptor (TLR) expression, and TLR agonist-induced alpha interferon secretion were analyzed. Patients with recurrent HSV-2 meningitis had elevated T cell blasting and Th1 and Th2 cytokine production in response to HSV antigens compared to those of patients with recurrent genital infections. A somewhat increased NK cell response, increased dendritic cell expression of TLR3 and -9, and increased TLR-induced alpha interferon responses were also noted. Contrary to our expectation, recurrent HSV-2 meningitis patients have increased HSV-specific adaptive and innate immune responses, raising the possibility of immune-mediated pathology in the development of recurrent HSV2 meningitis.
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| 10. |
- Lundqvist, Johanna, 1975-, et al.
(författare)
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Differentierad undervisning och integrerade digitala verktyg i förskola och skola: En storskalig studie
- 2021
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Ingår i: Utbildning och Lärande / Education and Learning. - Falun : Högskolan Dalarna. - 2001-4554. ; 15:3, s. 9-31
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Tidskriftsartikel (refereegranskat)abstract
- In Swedish preschool and school classrooms, all children should be offered an education that includes instruction and digital devices. The instruction should be meaningful and interesting for all children, and the digital devices should facilitate teachers’ work and children’s learning. This study concerns differentiated instruction as well as uses and possible benefits gained by digital devices in Swedish preschools and school classrooms. The study is part of a large-scale co-production project between academy and the surrounding society. Sixty-seven teachers and head-teachers, who value digital devices, participated, and shared their experiences and views on these two matters. A qualitative research approach, including research circles and thematic analyses, was used. The themes prove, for example, the importance of acknowledging children’s interests, joint exploration, provision of parallel support as well as extra challenges, association to children’s previous experiences and integration of digital devices of various kind. The result of the study can form a basis for interesting preschool and school discussions. It has relevance for teachers and head-teachers in training, researchers in special education as well as for those who are interested in differentiated instruction and the integration of digital devices.
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| 11. |
- Rydja, Johanna, 1972-
(författare)
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Gait Characteristics, Physical Activity and Subjective Outcome after Shunt Surgery in Normal Pressure Hydrocephalus
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background Idiopathic normal pressure hydrocephalus (iNPH) is a common but under-diagnosed disease among the elderly. The condition is characterised by gait disturbance, postural instability, cognitive decline and incontinence, caused by accumulated cerebrospinal fluid within the central nerve system. The treatment is a shunt insertion to divert excess fluid. Few studies have described the detailed gait in INPH, there is a lack of research about physical activity, and patient-reported outcomes after shunt surgery are sparsely described. The overall aim of this thesis was to increase the knowledge of the gait pattern, the level of physical activity, and to evaluate the effect of a physical exercise programme in iNPH. Another aim was to evaluate the patient’s self-experienced outcome after surgery. Methods and results, study I In total 127 patients were randomised to either a supervised 12-week high-intensity exercise programme or to standard care after shunt surgery. Evaluation was performed with the iNPH scale and goal attainment after the intervention and after six months. There was low compliance to the exercise programme and no differences between the groups could be detected according to the iNPH scale at any of the follow-ups. Patients with high attendance rate achieved their set goals to a higher extent than the control group at the post intervention follow-up. Methods and results, study II In total 109 patients from the population in study I, were evaluated with an actigraphy recording of physical activity variables for seven days before and three- and six months after shunt surgery. In addition, physical performance was evaluated with the 10-meter walk test, the 6-minute walk test and 30 s chair stand test. The patients walked faster with improved results on the walking tests postoperatively. Improvement in the 30 s chair stand test was interpreted as improved postural control. The physical activity intensity was not affected by surgery. The patients had very low energy expenditure and were to a large extent sedentary, before and after shunt surgery. The exercise intervention had no effect on physical activity or the physical performance tests. Methods and results, study III In total 47 patients were included to a gait analysis with an inertial sensor system. Additionally, the patients were assessed with the Timed Up and Go test and the iNPH scale, pre- and three months postoperatively and in relation with 42 older healthy individuals. The patients walked with shorter strides, decreased velocity, increased time in stance and with decreased joint angles, especially in the ankle joint. The gait pattern im-proved after shunt surgery, but outcome on all variables were still worse compared to the healthy individuals, except for step hight that was normalised. Shunt surgery had no effect on stride length variability. Methods and results, study IV In total 58 patients rated their experienced changes three months after shunt surgery. The subjective outcome was analysed in relation to objective clinical outcomes (the iNPH scale) and questionnaires regarding, sense of coherence, quality of life, anxiety and depression. Clinical outcome and the questionnaires were evaluated before and three months after shunt surgery and in relation to 42 older healthy individuals. The patients reported most frequently some degree of positive changes after surgery. The subjective outcomes in overall experience, gait and continence correlated moderately with the corresponding objective outcomes, but there were not correlations within the cognition and balance areas. Depression and quality of life improved after surgery, but the result was still lower than for healthy individuals. There was no correlation between the patients´ sense of coherence and the subjective outcome. Conclusion Shunt surgery contributes to improved walking patterns, improved physical functions, reduced signs of depression and increased quality of life, but patients with iNPH are still more affected than healthy elderly. The patients report most frequently positive changes, but not total recovery after shunt surgery. Despite improvements within several areas the physical activity level is very low, both before and after the shunt operation. A postoperative high-intensity physical training program had no additional effect, which is explained by the fact that few patients completed the program. Patients with iNPH probably need guidance to additional improvement and to increase physical activity through meaningful activities after shunt surgery. Further research is needed to evaluate interventions that address the specific iNPH impairments.
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| 12. |
- Öhlund, Malin, et al.
(författare)
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Laser Microdissection of Pancreatic Islets Allows for Quantitative Real-Time PCR Detection of Islet-Specific Gene Expression in Healthy and Diabetic Cats
- 2014
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Ingår i: Journal of Gastroenterology, Pancreatology & Liver Disorders. - : Symbiosis Open Access. - 2374-815X. ; 1:4, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Feline diabetes mellitus shares many similarities with human type 2 diabetes mellitus, including clinical, physiological and pathological features of the disease. The domestic cat spontaneously develops diabetes associated with insulin resistance in their middle age or later, with residual but declining insulin secretion. Humans and cats share largely the same environment and risk factors for diabetes, such as obesity and physical inactivity. Moreover, amyloid formation and loss of beta cells are found in the islets of the diabetic cat, as in humans. Altogether, the diabetic cat is a good model for type 2 diabetes in humans. The aims of the present study were to isolate feline islets using laser microdissection and to develop a quantitative method for detection of mRNA levels in islets of healthy and diabetic cats.Results: By using the laser microdissection technique, we were able to meticulously sample islets from both healthy and diabetic cats. Insulin staining of separate sections showed many beta cells in islets from healthy cats, whereas few insulin positive cells were found in islets from diabetic cats. By quantitative real-time PCR, mRNA levels of the islet-specific genes INS, PDX1, IAPP, CHGA and IA-2could be detected in both healthy and diabetic cats.Conclusions: Laser microdissection allows distinct studies of islets without contamination of acinar cells. Previous attempts in isolating feline islets with different collagenase-based protocols have led to damaged islets or islets coated with exocrine acinar cells, which either way compromise the results obtained from gene expression studies. The use of the laser microdissection technique eliminates these problems as shown in this study. Differences in gene expression between healthy and diabetic cats can reveal underlying mechanisms for beta cell dysfunction and decreased beta cell mass in human type 2 diabetes.
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