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- deSchoolmeester, J., et al.
(författare)
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Differences between men and women in the regulation of adipose 11 beta-HSD1 and in its association with adiposity and insulin resistance
- 2013
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Ingår i: Diabetes, obesity and metabolism. - : Wiley-Blackwell. - 1462-8902 .- 1463-1326. ; 15:11, s. 1056-1060
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Tidskriftsartikel (refereegranskat)abstract
- This study explored sex differences in 11-hydroxysteroid dehydrogenase type 1 (11-HSD1) activity and gene expression in isolated adipocytes and adipose tissue (AT), obtained via subcutaneous biopsies from non-diabetic subjects [58 M, 64 F; age 48.3 +/- 15.3years, body mass index (BMI) 27.2 +/- 3.9kg/m(2)]. Relationships with adiposity and insulin resistance (IR) were addressed. Males exhibited higher 11-HSD1 activity in adipocytes than females, but there was no such difference for AT. In both men and women, adipocyte 11-HSD1 activity correlated positively with BMI, waist circumference, % body fat, adipocyte size and with serum glucose, triglycerides and low-density lipoprotein:high-density lipoprotein (LDL:HDL) ratio. Positive correlations with insulin, HOMA-IR and haemoglobin A1c (HbA1c) and a negative correlation with HDL-cholesterol were significant only in males. Conversely, 11-HSD1 activity in AT correlated with several markers of IR and adiposity in females but not in males, but the opposite pattern was found with respect to 11-HSD1 mRNA expression. This study suggests that there are sex differences in 11-HSD1 regulation and in its associations with markers of obesity and IR.
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- Pereira, Maria J, 1981-, et al.
(författare)
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FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance
- 2014
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Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 63:9, s. 1198-1208
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Tidskriftsartikel (refereegranskat)abstract
- Objective To study effects of dexamethasone on gene expression in human adipose tissue aiming to identify potential novel mechanisms for glucocorticoid-induced insulin resistance. Materials/methods Subcutaneous and omental adipose tissue, obtained from non-diabetic donors (10 M/15 F; age: 28-60 years; BMI: 20.7-30.6 kg/m2), was incubated with or without dexamethasone (0.003-3 μmol/L) for 24 h. Gene expression was assessed by microarray and real time-PCR and protein expression by immunoblotting. Results FKBP5 (FK506-binding protein 5) and CNR1 (cannabinoid receptor 1) were the most responsive genes to dexamethasone in both subcutaneous and omental adipose tissue (~ 7-fold). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots. The gene product, FKBP51 protein, was 10-fold higher in the omental than in the subcutaneous depot, whereas the mRNA levels were similar. Higher FKBP5 gene expression in omental adipose tissue was associated with reduced insulin effects on glucose uptake in both depots. Furthermore, FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter and negatively with plasma HDL-cholesterol. FKBP5 SNPs were found to be associated with type 2 diabetes and diabetes-related phenotypes in large population-based samples. Conclusions Dexamethasone exposure promotes expression of FKBP5 in adipose tissue, a gene that may be implicated in glucocorticoid-induced insulin resistance. © 2014 Elsevier Inc.
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- Svensson, M.K, 1965, et al.
(författare)
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The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors
- 2015
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Ingår i: Diabetes-Metabolism Research and Reviews. - : Wiley. - 1520-7560 .- 1520-7552. ; 31:2, s. 138-146
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Tidskriftsartikel (refereegranskat)abstract
- AimsThe main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34years). MethodsAll 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. ResultsAfter median 17years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1kg/m(2)), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p=0.041), BMI (p=0.012) and HbA1c (p<0.001) were significant predictors of developing diabetic nephropathy between 9 and 17years of diabetes. At 17years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.051.12 per 1mmHg increase) were associated with DN. ConclusionsPatients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9years of follow-up was a risk marker for later development of diabetic nephropathy. Copyright (c) 2014 John Wiley & Sons, Ltd.
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- Pereira, Maria J., et al.
(författare)
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A Case Report of Improved Metabolic Control After Conversion From Everolimus to Cyclosporin A : Role of Adipose Tissue Mechanisms?
- 2014
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Ingår i: Transplantation Proceedings. - : Elsevier BV. - 0041-1345 .- 1873-2623. ; 46:7, s. 2377-2380
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Tidskriftsartikel (refereegranskat)abstract
- Background. New-onset diabetes after transplantation is associated with an increase in risk of graft failure, cardiovascular disease, and mortality. Therefore, it compromises the overall beneficial outcome of organ transplantation. Case Report. A patient with new-onset diabetes after renal transplantation showed glucose and lipid metabolism improvements after switching immunosuppressant from everolimus to cyclosporin A. A subcutaneous adipose tissue biopsy displayed changes in gene and protein expression that could contribute to the clinical improvement of hyperglycemia and dyslipidemia.
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