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Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulin-sensitive subjects.

Abstract：

AIMS/HYPOTHESIS:We determined the response of selected genes to in vivo insulin in adipose tissue in 21 non-diabetic women. MATERIALS AND METHODS:The women were divided into insulin-sensitive and -resistant groups based on their median whole-body insulin sensitivity (8.7+/-0.4 vs 4.2+/-0.3 mg kg(-1) min(-1) for insulin-sensitive vs -resistant group). Subcutaneous adipose tissue biopsies were obtained before and after 3 and 6 h of i.v. maintained euglycaemic hyperinsulinaemia. Adipose tissue mRNA concentrations of facilitated glucose transporter, member 1 (SLC2A1, previously known as GLUT1), facilitated glucose transporter, member 4 (SLC2A4, previously known as GLUT4), peroxisome proliferator-activated receptor gamma ( PPARG), peroxisome proliferator-activated receptor gamma co-activator 1alpha (PPARGC1A), 11beta-hydroxysteroid dehydrogenase-1 (HSD11B1), TNF, adiponectin (ADIPOQ), IL6 and the macrophage marker CD68 were measured using real-time PCR. RESULTS:Basal expression of 'insulin-sensitivity genes' SLC2A4 and ADIPOQ was lower while that of 'insulin-resistance genes', HSD11B1 and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. Insulin significantly increased expression of 'insulin-sensitivity genes' SLC2A4, PPARG, PPARGC1A and ADIPOQ in the insulin-sensitive group, while only expression of PPARG and PPARGC1A was increased in the insulin-resistant group. The expression of 'insulin-resistance genes' HSD11B1 and IL6 was increased by insulin in the insulin-resistant group, but insulin failed to increase HSD11B1 expression in the insulin-sensitive group. At 6 h, expression of HSD11B1, TNF and IL6 was significantly higher in the insulin-resistant than in the insulin-sensitive group. IL6 expression increased significantly more in response to insulin in the insulin-resistant than in the insulin-sensitive group. CD68 was overexpressed in the insulin-resistant as compared with the insulin-sensitive group at both 0 and 6 h. CONCLUSIONS/INTERPRETATION:These data suggest that genes adversely affecting insulin sensitivity hyperrespond to insulin, while genes enhancing insulin sensitivity hyporespond to insulin in insulin-resistant human adipose tissue in vivo.

journal_name

Diabetologia

journal_title

Diabetologia

authors

Westerbacka J,Cornér A,Kannisto K,Kolak M,Makkonen J,Korsheninnikova E,Nyman T,Hamsten A,Fisher RM,Yki-Järvinen H

doi

10.1007/s00125-005-0075-5

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

132-40

issue

eissn

0012-186X

issn

1432-0428

journal_volume

pub_type

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Acute in vivo effects of insulin on gene expression in adipose tissue in insulin-resistant and insulin-sensitive subjects.