Insulin Treatment Reverses the Insulin Resistance of Type II Diabetes Mellitus
Insulin Treatment Reverses the Insulin Resistance of Type II Diabetes Mellitus
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胰岛素治疗可逆转 II 型糖尿病的胰岛素抵抗
DOI：
10.2337/diacare.5.4.353
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发表时间：
1982
期刊：
影响因子：
16.2
通讯作者：
O. Kolterman
中科院分区：
文献类型：
--
作者：
J. A. Scarlett;R. S. Gray;J. Griffin;J. Olefsky;O. Kolterman
II型糖尿病受试者是胰岛素缺乏和胰岛素抵抗的。最近的研究表明，胰岛素抵抗是由于受体和受体后缺陷的联合作用，其中受体后缺陷是主要的损害。在本研究中，我们研究了外源性胰岛素治疗对6例未经治疗的II型糖尿病患者胰岛素作用缺陷的影响。在治疗前，测量血糖控制和脂肪细胞胰岛素结合，并构建总体葡萄糖处置和肝脏葡萄糖输出抑制的体内胰岛素剂量-反应曲线。在这些初步研究之后，糖尿病受试者接受了14天的常规和NPH纯化猪胰岛素每日两次注射治疗，并重复了预处理研究。该治疗方案显著改善了血糖控制。平均空腹血糖水平（± SE）从287 ± 20 mg/dl降至125 ± 13 mg/dl，平均糖化血红蛋白水平（± SE）从14.2 ± 1.1%降至8.3 ± 0.5%，平均24小时尿糖排泄量（± SE）从65.6 ± 40.3降至0.6 ± 0. 1 g/24 h。在治疗期间，脂肪细胞胰岛素结合没有显著变化。与此相反，胰岛素治疗14天后，胰岛素刺激的葡萄糖最大处置速率为321 ± 32 mg/M2/min，较治疗前的187 ± 32 mg/M2/min增加了72%（P <0.005），表明胰岛素作用的受体后缺陷被胰岛素治疗显著改善。胰岛素介导的肝葡萄糖输出抑制的剂量-反应曲线右移，与胰岛素结合减少一致，治疗前最大效应未降低，胰岛素治疗后无显著变化。总之，胰岛素刺激的葡萄糖处置中的受体后缺陷在很大程度上通过外源性胰岛素治疗得到改善，这表明胰岛素作用中的这种缺陷是继发于胰岛素缺乏状态的某些方面的获得性异常。
Type II diabetic subjects are both insulin-deficient and insulin-resistant. Recent studies suggest that the insulin resistance is due to a combined receptor and postreceptor defect with the postreceptor defect being the predominant lesion. In the present study, we examined the effects of exogenous insulin therapy upon these defects in insulin action in six untreated type II diabetic subjects. Glycemic control and adipocyte insulin binding were measured and in vivo insulin dose-response curves for overall glucose disposal and suppression of hepatic glucose output were constructed before treatment. Following these initial studies, the diabetic subjects were treated with twice-daily injections of regular and NPH purified pork insulin for 14 days and the pretreatment studies repeated. Glycemic control was significantly improved by this treatment regimen. The mean fasting serum glucose level (±SE) fell from 287 ± 20 to 125 ± 13 mg/dl, the mean glycosylated hemoglobin level (± SE) decreased from 14.2 ± 1.1% to 8.3 ± 0.5%, and the mean 24-h urinary glucose excretion (±SE) declined from 65.6 ± 40.3 to 0.6 ± 0. 1 g/24 h. Adipocyte insulin binding did not change significantly during the treatment period. In contrast, the 14-day period of insulin treatment produced a 72% increase (P < 0.005) in the maximal rate of insulin-stimulated glucose disposal, 321 ± 32 mg/M2/min compared with 187 ± 32 mg/M2/min before treatment, indicating that the postreceptor defect in insulin action was significantly ameliorated by insulin treatment. The dose-response curve for insulin-mediated suppression of hepatic glucose output was rightshifted, consistent with the decrease in insulin binding, with no decrease in the maximal effect before treatment and not significantly changed following insulin treatment. In conclusion, the postreceptor defect in insulin-stimulated glucose disposal is largely ameliorated by exogenous insulin treatment, suggesting that this defect in insulin action is an acquired abnormality which is secondary to some aspect of the insulin-deficient state.