Mai K, Kullmann V, Bobbert T, Maser-Gluth C, Möhlig M, Bähr V, Pfeiffer A F H, Spranger J, Diederich S
Department of Endocrinology, Diabetes and Nutrition, Charite Humanmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
Clin Endocrinol (Oxf). 2005 Oct;63(4):442-9. doi: 10.1111/j.1365-2265.2005.02362.x.
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 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), accompanied by elevated hepatic cortisol levels.
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 11beta-HSD1 activity, plasma cortisol levels were measured after oral administration of cortisone acetate during lipid or saline infusion. In addition, 11beta-HSD activities were determined in vivo by calculating the urinary ratios of GC metabolites.
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 11beta-HSD1 activity were found, neither by changes in cortisone acetate to cortisol conversion nor by differences in urinary free cortisol (UFF) or cortisone (UFE), 5beta-tetrahydrocortisol (THF), 5alpha-THF, cortisone (THE), UFF/UFE and (5alpha-THF + THF)/THE ratios.
We found no change in hepatic and whole-body 11beta-HSD1 activity during acute FFA-induced insulin resistance. Further studies are necessary to clarify whether 11beta-HSD1 in muscle and adipose tissue is influenced by FFAs and whether 11beta-HSD1 is involved in other conditions of insulin resistance.
游离脂肪酸（FFA）可诱导肝脏胰岛素抵抗并增强肝脏糖异生作用。糖皮质激素（GC）也会刺激肝脏糖异生。本研究的目的是探究FFA诱导的肝脏胰岛素抵抗是否由肝脏11β-羟基类固醇脱氢酶1型（11β-HSD1）活性增加介导，并伴有肝脏皮质醇水平升高。
在10小时夜间禁食后，对6名健康男性志愿者进行研究。在输注脂质或生理盐水期间进行正常血糖高胰岛素钳夹试验。为评估肝脏11β-HSD1活性，在输注脂质或生理盐水期间口服醋酸可的松后测量血浆皮质醇水平。此外，通过计算GC代谢产物的尿比值在体内测定11β-HSD活性。
输注脂质使FFA增加（5.41±1.00对0.48±0.20 mmol/l；P<0.005），并显著增加胰岛素抵抗[葡萄糖输注速率（GIR）6.02±2.60对4.
