Insulin action on adipose genes in diabetes - Diabetes

Nutrition Research Newsletter, Feb, 2004

Evidence is emerging that there is a coordinated dysregulation of genes along metabolic pathways important for insulin action in type 2 diabetes. Adipose tissue secretes several molecules that may participate in metabolic cross-talk to other insulin-sensitive tissues. Therefore, adipose tissue is a key endocrine organ that regulates insulin sensitivity in other peripheral insulin target tissues.

The enzyme 11b-hydroxysteroid dehydrogenase type-1 (11b-HSD-1) catalyzes the interconversion of cortisone to active cortisol. Overexpression of 11b-HSD-1, specifically in adipose tissue, leads to visceral obesity and insulin resistance. Sterol regulatory element binding protein 1-c (SREBP-1C) is a transcription factor that regulates the expression of numerous genes involved in glucose and lipid metabolism. A group of Swedish researchers examined whether the express and acute insulin regulation of adiponectin, c-Cbl-associated protein (CAP), 11b-HSD-1, and SREP-1c are altered in subcutaneous adipose tissue from type 2 diabetic subjects.

Type 2 diabetic and non-diabetic (control) men were matched for age, BMI, percentage of body fat, and physical fitness. Expression of adiponectin, CAP, 11b-HSD-1, and SREBP-1C was determined in subcutaneous adipose tissue by real-time polymerase chain reaction analysis. Whole body insulin-stimulated glucose disposal was determined using the euglycemic hyperinsulinemic clamp technique.

The glucose infusion rate needed to maintain euglycemia was 50% lower in type 2 diabetic subjects. Expression of adiponectin, CAP, 11b-HSD-1, and SREBP-1C was similar between the healthy controls and type 2 diabetic subjects. Insulin infusion for three hours did not affect expression of CAP, 11b-HSD-1, or adiponectin mRNA in either group. However, insulin infusion increased the expression of SREBP-1c mRNA 80% in the non-diabetic controls but not in the type 2 diabetics.

The results show that insulin action on SREBP-1C is dysregulated in adipose tissue from type 2 diabetic subjects. Therefore, defects in insulin regulation of gene expression of select targets are likely to contribute to the pathogenesis of type 2 diabetes.

Heikki A. Koistinen, Margareta Forsgren, Harriet Wallberg-Henriksson, et al. Insulin action on expression of novel adipose genes in health and type 2 diabetic subjects. Obesity Research 12(1): 25-31 (January 2004) [Correspondence: Juleen R. Zierath, Department of Surgical Sciences, Section for Integrative Physiology, Karolinska Institute, von Eulers vag 4, 2 tr, 17177 Stockholm, Sweeden. E-mail: juleen.zierath@fyfa.ki.se.]