Affiliation:
1. Institut National de la Santé et de la Recherche Médicale (INSERM) U.449 and
2. Human Nutrition Research Center of Lyon, Faculty of Medicine R. Laennec
3. Department of Endocrinology, Diabetology, and Nutrition, E. Herriot Hospital, Lyon, France
Abstract
Defective regulation of gene expression may be involved in the pathogenesis of type 2 diabetes. We have characterized the concerted regulation by insulin (3-h hyperinsulinemic clamp) of the expression of 10 genes related to insulin action in skeletal muscle and in subcutaneous adipose tissue, and we have verified whether a defective regulation of some of them could be specifically encountered in tissues of type 2 diabetic patients. Basal mRNA levels (determined by reverse transcriptase–competitive polymerase chain reaction) of insulin receptor, insulin receptor substrate-1, p85α phosphatidylinositol 3-kinase (PI3K), p110αPI3K, p110βPI3K, GLUT4, glycogen synthase, and sterol regulatory-element-binding protein-1c (SREBP-1c) were similar in muscle of control (n = 17), type 2 diabetic (n = 9), type 1 diabetic (n = 9), and nondiabetic obese (n = 9) subjects. In muscle, the expression of hexokinase II was decreased in type 2 diabetic patients (P < 0.01). In adipose tissue, SREBP-1c (P < 0.01) mRNA expression was reduced in obese (nondiabetic and type 2 diabetic) subjects and was negatively correlated with the BMI of the subjects (r = −0.63, P = 0.02). Insulin (±1,000 pmol/l) induced a two- to threefold increase (P < 0.05) in hexokinase II, p85αPI3K, and SREBP-1c mRNA levels in muscle and in adipose tissue in control subjects, in insulin-resistant nondiabetic obese patients, and in hyperglycemic type 1 diabetic subjects. Upregulation of these genes was completely blunted in type 2 diabetic patients. This study thus provides evidence for a specific defect in the regulation of a group of important genes in response to insulin in peripheral tissues of type 2 diabetic patients.
Publisher
American Diabetes Association
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
236 articles.
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