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Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes.
Diabetes 2001; 50(5):1134-42D

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, p85alpha phosphatidylinositol 3-kinase (PI3K), p110alphaPI3K, p110betaPI3K, 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, p85alphaPI3K, 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.

Authors+Show Affiliations

Institut National de la Santé et de la Recherche Médicale INSERM U.449, Faculty of Medicine R. Laennec, Lyon, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11334418

Citation

Ducluzeau, P H., et al. "Regulation By Insulin of Gene Expression in Human Skeletal Muscle and Adipose Tissue. Evidence for Specific Defects in Type 2 Diabetes." Diabetes, vol. 50, no. 5, 2001, pp. 1134-42.
Ducluzeau PH, Perretti N, Laville M, et al. Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes. Diabetes. 2001;50(5):1134-42.
Ducluzeau, P. H., Perretti, N., Laville, M., Andreelli, F., Vega, N., Riou, J. P., & Vidal, H. (2001). Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes. Diabetes, 50(5), pp. 1134-42.
Ducluzeau PH, et al. Regulation By Insulin of Gene Expression in Human Skeletal Muscle and Adipose Tissue. Evidence for Specific Defects in Type 2 Diabetes. Diabetes. 2001;50(5):1134-42. PubMed PMID: 11334418.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation by insulin of gene expression in human skeletal muscle and adipose tissue. Evidence for specific defects in type 2 diabetes. AU - Ducluzeau,P H, AU - Perretti,N, AU - Laville,M, AU - Andreelli,F, AU - Vega,N, AU - Riou,J P, AU - Vidal,H, PY - 2001/5/4/pubmed PY - 2001/5/25/medline PY - 2001/5/4/entrez SP - 1134 EP - 42 JF - Diabetes JO - Diabetes VL - 50 IS - 5 N2 - 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, p85alpha phosphatidylinositol 3-kinase (PI3K), p110alphaPI3K, p110betaPI3K, 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, p85alphaPI3K, 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. SN - 0012-1797 UR - https://www.unboundmedicine.com/medline/citation/11334418/Regulation_by_insulin_of_gene_expression_in_human_skeletal_muscle_and_adipose_tissue__Evidence_for_specific_defects_in_type_2_diabetes_ L2 - http://diabetes.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=11334418 DB - PRIME DP - Unbound Medicine ER -