Literature DB >> 16362280

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

J Westerbacka1, A Cornér, K Kannisto, M Kolak, J Makkonen, E Korsheninnikova, T Nyman, A Hamsten, R M Fisher, H Yki-Järvinen.   

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.

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Year:  2005        PMID: 16362280     DOI: 10.1007/s00125-005-0075-5

Source DB:  PubMed          Journal:  Diabetologia        ISSN: 0012-186X            Impact factor:   10.122


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