CORTISOL-INDUCED INSULIN RESISTANCE IN MAN - IMPAIRED SUPPRESSION OF GLUCOSE-PRODUCTION AND STIMULATION OF GLUCOSE-UTILIZATION DUE TO A POSTRECEPTOR DEFECT OF INSULIN ACTION
CORTISOL-INDUCED INSULIN RESISTANCE IN MAN - IMPAIRED SUPPRESSION OF GLUCOSE-PRODUCTION AND STIMULATION OF GLUCOSE-UTILIZATION DUE TO A POSTRECEPTOR DEFECT OF INSULIN ACTION
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DOI：
10.1210/jcem-54-1-131
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发表时间：
1982-01-01
影响因子：
5.8
通讯作者：
GERICH, JE
中科院分区：
文献类型：
--
作者：
RIZZA, RA;MANDARINO, LJ;GERICH, JE
本研究探讨了皮质醇诱导的胰岛素抵抗的机制，测定了6名正常志愿者在24 h内输注皮质醇和24 h内输注生理盐水后，胰岛素抑制葡萄糖产生和刺激葡萄糖利用的量效特征及其与单核细胞和红细胞胰岛素受体结合的关系。皮质醇的输注（2 μ g kg-1 min-1）使血浆皮质醇浓度增加约4倍（37 ± 0.5 μ g kg-1 min-1）。3对14 +-。1 μ g/dl;这种高皮质醇血症增加了吸收后血浆葡萄糖（126 . ±. P < 0.01）。2比97 +-。2 mg/dl; P < 0.01）和血浆胰岛素（16 . ±. 2对10 +-。2 μ U/ml; P < 0.01）葡萄糖产生的浓度和速率（2.4 ± 0.01）。0.1 vs. 2.1 .+-。-0.1 mg kg-1 min-1; P < 0.01）和利用（2.5 . ±. 0.1 vs. 2.1 .+-。0.1 mg kg ~（-1）min ~（-1）; P < 0.01）。两种葡萄糖产生抑制的胰岛素剂量-反应曲线（在81 ± 0.5mg/kg时的半最大反应）。19对31 +-。5 μ U/ml; P < 0.05）和葡萄糖利用的刺激（在104 ± 0.5 μ U/ml时的半最大反应）。9对64 +-。7 μ U/ml; P < 0.01）向右移动，保留了对胰岛素的正常最大反应。单核细胞和红细胞胰岛素结合均未降低。除了在接近最大胰岛素受体占有率时，胰岛素对葡萄糖产生和利用的作用降低，单位数量的单核细胞和红细胞胰岛素受体占有。显然，皮质醇诱导的胰岛素抵抗是由于肝脏和肝外对胰岛素的敏感性降低。假设胰岛素与单核细胞和红细胞的结合反映了胰岛素在胰岛素敏感组织中的结合，那么这种胰岛素作用的降低可以根据受体后缺陷来解释。
The present studies assessed the mechanisms responsible for cortisol-induced insulin resistance in man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose utilization and their relationship to monocyte and erythrocyte insulin receptor binding were determined in 6 normal volunteers after 24-h infusion of cortisol and 24-h infusion of saline. The infusion of cortisol (2 .mu.g kg-1 min-1) increased the plasma cortisol concentration approximately 4-fold (37 .+-. 3 vs. 14 .+-. 1 .mu.g/dl; P < 0.01) to values observed during moderately severe stress in man. This hypercortisolemia increased postabsorptive plasma glucose (126 .+-. 2 vs. 97 .+-. 2 mg/dl; P < 0.01) and plasma insulin (16 .+-. 2 vs. 10 .+-. 2 .mu.U/ml; P < 0.01) concentrations and rates of glucose production (2.4 .+-. 0.1 vs. 2.1 .+-. -0.1 mg kg-1 min-1; P < 0.01) and utilization (2.5 .+-. 0.1 vs. 2.1 .+-. 0.1 mg kg-1 min-1; P < 0.01). Insulin dose-response curves for both suppression of glucose production (half-maximal response at 81 .+-. 19 vs. 31 .+-. 5 .mu.U/ml; P < 0.05) and stimulation of glucose utilization (half-maximal response at 104 .+-. 9 vs. 64 .+-. 7 .mu.U/ml; P < 0.01) were shifted to the right, with preservation of normal maximal responses to insulin. Neither monocyte nor erythrocyte insulin binding was decreased. Except at near-maximal insulin receptor occupancy, the action of insulin on glucose production and utilization per number of monocyte and erythrocyte insulin receptors occupied was decreased. Evidently the cortisol-induced insulin resistance in man is due to a decrease in both hepatic and extrahepatic sensitivity to insulin. Assuming that insulin binding to monocytes and erythrocytes reflects insulin binding in insulin-sensitive tissues, this decrease in insulin action can be explained on the basis of a postreceptor defect.