ECE2008 Poster Presentations Obesity (94 abstracts)
Introduction: 11β-hydroxysteroid dehydrogenase type 1 (11 β-HSD1) converts cortisone into its active metabolite, cortisol. Mechanisms regulating the promoter-activity of 11β-HSD1 are of considerable importance to understand the basics of intracellular cortisol, lipid and glucose metabolism. The incretine glucose-dependent insulinotropic polypeptide (GIP) has been suggested to affect insulin sensitivity. However, the mechanisms of this effect are unclear yet.
Objectives and Settings: We aimed to analyse the effect of GIP on 11β-HSD1 enzyme activity and mRNA level in adipose tissue. Therefore fat biopsies of 10 healthy overweight men (BMI: 2840 kg/m2; age: 3065 years) with a normal glucose tolerance were taken before and after a GIP or saline infusion over 4 h. Enzyme activity of 11β-HSD1 was measured and qRT-PCR was performed to determine the gene expression level of 11β-HSD1. Effects of GIP on 11β-HSD1 promoter activity were analysed using 11β-HSD1-Luciferase promoter constructs in 3T3-L1 cells.
Results: GIP reduced mRNA-expression and activity by approximately 30% (P<0.05). Comparably, the promoter activity of 11β-HSD1 as measured by Luciferase activity and the mRNA-expression of 11β-HSD1 was substantially reduced by GIP in differentiated 3T3-L1 cells.
Conclusion: We demonstrated that GIP downregulates the expression and activity of 11β-HSD1 in adipose tissue in vivo and in vitro. Thus, GIP might affect fat metabolism via inhibition of 11β-HSD1.