In vivo activity of 11β-hydroxysteroid dehydrogenase type 1 and free fatty acid-induced insulin resistance
Free fatty acids (FFAs) induce hepatic insulin resistance and enhance hepatic gluconeogenesis. Glucocorticoids (GCs) also stimulate hepatic gluconeogenesis. The aim of this study was to investigate whether the FFA-induced hepatic insulin resistance is mediated by increased activity of hepatic 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), accompanied by elevated hepatic cortisol levels. Methods
Following a 10-h overnight fast, six healthy male volunteers were investigated. A euglycaemic hyperinsulinaemic clamp was performed during lipid or saline infusion. To assess hepatic 11β-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11β-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites. Results
Lipid infusion increased FFAs (5·41 ± 1·00 vs. 0·48 ± 0·20 mmol/l; P < 0·005) and significantly increased insulin resistance [glucose infusion rate (GIR) 6·02 ± 2·60 vs. 4·08 ± 2·15 mg/kg/min; P < 0·005]. After lipid and saline infusions no changes in 11β-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5β-tetrahydrocortisol (THF), 5α-THF, cortisone (THE), UFF/UFE and (5α-THF + THF)/THE ratios. Conclusions
We found no change in hepatic and whole-body 11β-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11β-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11β-HSD1 is involved in other conditions of insulin resistance.
Document Type: Research Article
Affiliations: 1: Department of Endocrinology, Diabetes and Nutrition, Charite Humanmedizin Berlin, Campus Benjamin Franklin, Berlin and Department of Clinical Nutrition, German Institute of Human Nutrition Potsdam, Bergholz-Rehbrücke, 2: Steroid Laboratory, Department of Pharmacology, Rupprecht-Karls-University of Heidelberg, Heidelberg, Germany
Publication date: October 1, 2005