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

• Published in: Diabetologia Vol. 49; no. 1; pp. 132 - 140
• Main Authors: Westerbacka, J, Cornér, A, Kannisto, K, Kolak, M, Makkonen, J, Korsheninnikova, E, Nyman, T, Hamsten, A, Fisher, R. M, Yki-Järvinen, H
• Format: Journal Article
• Language: English
• Published: Berlin Berlin/Heidelberg : Springer-Verlag 2006; Springer
• Subjects: adipokines; adiponectin; Adipose Tissue - drug effects; Adipose Tissue - physiology; Adolescent; Adult; Biological and medical sciences; Body Mass Index; Body Weight; cortisol; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Gene Expression Regulation - drug effects; Humans; Insulin - pharmacology; Insulin Resistance - physiology; interleukins; macrophages; Medical sciences; Medicin och hälsovetenskap; Middle Aged; PGC-1; Reference Values; TNF; Endocrinopathy; Human; Corticosteroid; Pancreatic hormone; Adipose tissue; Steroid hormone; Diabetes mellitus; Interleukin; Cytokine; Cortisol; Adipokine; Gene expression; Hydrocortisone; Macrophages; Glucocorticoid; Insulin; TNF; Adiponectin; Adipocytokines; In vivo; Tumor necrosis factor; Adrenal hormone; PGC-1; Macrophage
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-005-0075-5

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 γ ( PPARG), peroxisome proliferator-activated receptor γ co-activator 1α (PPARGC1A), 11β-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.