| 1. |
- Grunnet, Louise G., et al.
(författare)
-
Regulation and Function of FTO mRNA Expression in Human Skeletal Muscle and Subcutaneous Adipose Tissue
- 2009
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:10, s. 2402-2408
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Common variants in FTO (the fat mass- and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and nongenetic regulation of FTO mRNA in skeletal muscle and adipose tissue and their influence on in vivo glucose and fat metabolism. RESEARCH DESIGN AND METHODS-The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years) and elderly (58-66 years) nondiabetic twins examined by a hyperinsulinemic-euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n = 226) and skeletal muscle biopsies (n = 158). RESULTS-Heritability of FTO expression in both tissues was low, and FTO expression was not influenced by FTO rs9939609 genotype. FTO mRNA expression in skeletal muscle was regulated by age and sex, whereas age and BMI were predictors of adipose tissue FTO mRNA expression. FTO mRNA expression in adipose tissue was associated with an atherogenic lipid profile. In skeletal muscle, FTO mRNA expression was negatively associated to fat and positively to glucose oxidation rates as well as positively correlated with expression of genes involved in oxidative phosphorylation including PGC1 alpha. CONCLUSIONS-The heritability of FTO expression in adipose tissue and skeletal muscle is low and not influenced by obesity-associated FTO genotype. The age-dependent decline in FTO expression is associated with peripheral defects of glucose and fat metabolism. Diabetes 58:2402-2408, 2009
|
|
| 2. |
- Nilsson, Emma A, et al.
(författare)
-
Genetic and Nongenetic Regulation of CAPN10 mRNA Expression in Skeletal Muscle.
- 2005
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 54:10, s. 3015-3020
-
Tidskriftsartikel (refereegranskat)abstract
- The gene encoding calpain-10 (CAPN10) has been identified as a candidate gene for type 2 diabetes. Our aim was to study the impact of genetic (heritability and polymorphisms) and nongenetic (insulin, free fatty acids, and age) factors on CAPN10 mRNA expression in skeletal muscle using two different study designs. Muscle biopsies were obtained before and after hyperinsulinemic-euglycemic clamps from 166 young and elderly monozygotic and dizygotic twins as well as from 15 subjects with normal (NGT) or impaired glucose tolerance (IGT) exposed to an Intralipid infusion. We found hereditary effects on both basal and insulin-exposed CAPN10 mRNA expression. Carriers of the type 2 diabetes–associated single nucleotide polymorphism (SNP)-43 G/G genotype had reduced CAPN10 mRNA levels compared with subjects carrying the SNP-43 A-allele. Age had no significant influence on CAPN10 mRNA levels. Insulin had no significant effect on CAPN10 mRNA levels, neither in the twins nor in the basal state of the Intralipid study. However, after a 24-h infusion of Intralipid, we noted a significant increase in CAPN10 mRNA in response to insulin in subjects with NGT but not in subjects with IGT. In conclusion, we provide evidence that mRNA expression of CAPN10 in skeletal muscle is under genetic control. Glucose-tolerant but not glucose-intolerant individuals upregulate their CAPN10 mRNA levels in response to prolonged exposure to fat.
|
|
| 3. |
- Ribel-Madsen, Rasmus, et al.
(författare)
-
Retinol-Binding Protein 4 in Twins Regulatory Mechanisms and Impact of Circulating and Tissue Expression Levels on Insulin Secretion and Action
- 2009
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 58:1, s. 54-60
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Retinol-binding protein (RBP) 4 is an adipokine of which plasma levels are elevated in obesity and type 2 diabetes. The aims of the study were to identify determinants of plasma RBP4 and RBP4 mRNA expression in subcutaneous adipose tissue (SAT) and skeletal muscle and to investigate the association between RBP4 and in vivo measures of glucose metabolism. RESEARCH DESIGN AND METHODS-The study population included 298 elderly twins (aged 62-83 years), with glucose tolerance ranging from normal to overt type 2 diabetes, and 178 young (aged 25-32 years) and elderly (aged 58-66 years) nondiabetic twins. Peripheral and hepatic insulin sensitivity was assessed by a euglycemic-hyperinsulinemic clamp, and beta-cell function was estimated from an intravenous glucose tolerance test. RESULTS-The influence of environmental versus genetic factors in the regulation of plasma RBP4 increased with age. Plasma RBP4 was elevated in type 2 diabetes and increased with duration of disease. Plasma RBP4 correlated inversely with peripheral, but not hepatic, insulin sensitivity. However, the association disappeared after correction for covariates, including plasma. adiponectin. Plasma retinol, and not RBP4, was inversely associated with insulin secretion. SAT RBP4 expression correlated positively with GLUT4 expression and inversely with glucose tolerance. Skeletal muscle RBP4 expression reflected intramuscular fat, and although it was suppressed by insulin, no association with insulin sensitivity was evident. RBP4 expression was not associated with circulatory RBP4. CONCLUSIONS-In conclusion, our data indicate that, RBP4 levels in plasma, skeletal muscle, and fat may be linked to insulin resistance and type 2 diabetes in a secondary and noncausal manner. Diabetes 58:54-60, 2009
|
|
