Rooney D P, Neely R D, Cullen C, Ennis C N, Sheridan B, Atkinson A B, Trimble E R, Bell P M
Sir George E. Clark Metabolic Unit, B.S. Royal Victoria Hospital, Belfast, Northern Ireland.
J Clin Endocrinol Metab. 1993 Nov;77(5):1180-3. doi: 10.1210/jcem.77.5.8077310.
Increased glucose/glucose-6-phosphate (G/G6P) substrate cycle activity may be an early marker of disordered hepatic glucose metabolism. To investigate the effects of glucocorticoids on G/G6P cycle activity and insulin resistance, we studied eight normal subjects using the euglycemic glucose clamp technique with high pressure liquid chromatography-purified [2(3)H]- and [6-3H]glucose tracers at insulin infusion rates of 0.4 and 2.0 mU/kg.min after 24-h cortisol (2 micrograms/kg.min) and saline infusions. Endogenous glucose production ([6-3H]glucose) was greater after cortisol than saline in the postabsorptive state (13.3 +/- 0.5 vs. 12.2 +/- 0.5 mumol/kg.min; P < 0.05) and during 0.4-mU insulin infusion (10.5 +/- 0.7 vs. 5.0 +/- 0.8 mumol/kg.min; P < 0.005). During 2.0-mU insulin infusion, endogenous glucose production was suppressed similarly (5.1 +/- 0.4 vs. 4.1 +/- 0.5 mumol/kg.min), but glucose disappearance was less after cortisol than saline (38.7 +/- 3.5 vs. 64.6 +/- 4.3 mumol/kg.min; P < 0.001). G/G6P cycle activity after cortisol and saline was similar in the postabsorptive state and during 0.4 mU insulin. During 2.0 mU insulin, cycle activity was greater after cortisol than saline (3.6 +/- 0.9 vs. 0.8 +/- 0.5 mumol/kg.min; P < 0.005). In conclusion, cortisol induces hepatic insulin resistance without significantly changing G/G6P cycle activity. At high glucose turnover rates, G/G6P cycle activity is increased by cortisol; however, reduced glucose disappearance is the main cause of impaired insulin action.
葡萄糖/葡萄糖-6-磷酸（G/G6P）底物循环活性增加可能是肝脏葡萄糖代谢紊乱的早期标志。为了研究糖皮质激素对G/G6P循环活性和胰岛素抵抗的影响，我们使用正常血糖葡萄糖钳夹技术，在24小时输注皮质醇（2微克/千克·分钟）和生理盐水后，以0.4和2.0毫单位/千克·分钟的胰岛素输注速率，对8名正常受试者进行了研究，同时使用高压液相色谱纯化的[2(3)H]-和[6-3H]葡萄糖示踪剂。在空腹状态下（13.3±0.5对12.2±0.5微摩尔/千克·分钟；P<0.05）以及在输注0.4毫单位胰岛素期间（10.5±0.7对5.0±0.8微摩尔/千克·分钟；P<0.005），皮质醇输注后的内源性葡萄糖生成（[6-3H]葡萄糖）高于生理盐水输注后。在输注2.0毫单位胰岛素期间，内源性葡萄糖生成受到类似抑制（5.1±0.4对4.1±0.5微摩尔/千克·分钟），但皮质醇输注后的葡萄糖消失低于生理盐水输注后（38.7±3.5对64.6±4.3微摩尔/千克·分钟；P<0.001）。在空腹状态下以及输注0.4毫单位胰岛素期间，皮质醇和生理盐水后的G/G6P循环活性相似。在输注2.0毫单位胰岛素期间，皮质醇后的循环活性高于生理盐水后（3.6±0.9对0.8±0.5微摩尔/千克·分钟；P<0.005）。总之，皮质醇诱导肝脏胰岛素抵抗，但不显著改变G/G6P循环活性。在高葡萄糖周转率时，皮质醇会增加G/G6P循环活性；然而，葡萄糖消失减少是胰岛素作用受损的主要原因。
