DeFronzo R, Deibert D, Hendler R, Felig P, Soman V
J Clin Invest. 1979 May;63(5):939-46. doi: 10.1172/JCI109394.
Tissue sensitive to insulin and insulin binding to monocytes were evaluated in 15 nonobese maturity-onset diabetics and in 16 healthy controls. Insulin sensitivity was determined by the insulin clamp technique in which the plasma insulin is acutely raised and maintained 100 muU/ml above the fasting level and plasma glucose is held constant at fasting levels by a variable glucose infusion. The amount of glucose infused is a measure of overall tissue sensitivity to insulin. In the diabetic group, the fasting plasma glucose concentration (168+/-4 mg/dl) was 85% greater than controls (P < 0.01) whereas the plasma insulin level (15+/-1 muU/ml) was similar to controls. During the insulin clamp study, comparable plasma insulin levels were achieved in the diabetics (118+/-5) and the controls (114+/-5 muU/ml). However, the glucose infusion rate in the diabetics (4.7+/-0.4 mg/kg.min) was 30% below controls (P < 0.01). Among the diabetics, the glucose infusion rate correlated directly with the fasting plasma glucose level (r = 0.57, P < 0.05). In five diabetic subjects, glucose metabolism was similar to controls, and these diabetics had the highest fasting glucose levels. When they were restudied after prior normalization (with insulin) of the fasting plasma glucose (100+/-1 mg/dl), the glucose infusion rate during the insulin clamp was 30% lower than observed in association with hyperglycemia (P < 0.01). Studies that employed tritiated glucose to measure endogenous glucose production indicated comparable 90-95% inhibition of hepatic glucose production during hyperinsulinemia in the diabetic and control subjects.(125)I-insulin binding to monocytes in the diabetics (5.5+/-0.6%) was 30% below that in controls (P < 0.01). Insulin binding to monocytes and insulin action as determined with the insulin clamp were highly correlated in both control (r = 0.67, P < 0.01), and diabetic subjects (r = 0.88, P < 0.001). We conclude that (a) tissue sensitivity to physiologic hyperinsulinemia is reduced in most maturity-onset diabetics; (b) this decrease in sensitivity is located, at least in part, in extrahepatic tissues; (c) the resistance to insulin may be mediated by a reduction in insulin binding; and (d) in maturity-onset diabetics with normal tissue sensitivity to insulin, hyperglycemia may be a contributing factor to the normal rates of insulin-mediated glucose uptake.
在15名非肥胖型成年发病型糖尿病患者和16名健康对照者中，对胰岛素敏感组织以及胰岛素与单核细胞的结合情况进行了评估。胰岛素敏感性通过胰岛素钳夹技术测定，即急性升高血浆胰岛素水平并使其维持在高于空腹水平100 μU/ml，通过可变葡萄糖输注使血浆葡萄糖维持在空腹水平。输注的葡萄糖量是整体组织对胰岛素敏感性的一个指标。糖尿病组的空腹血浆葡萄糖浓度（168±4 mg/dl）比对照组高85%（P<0.01），而血浆胰岛素水平（15±1 μU/ml）与对照组相似。在胰岛素钳夹研究期间，糖尿病患者（118±5）和对照组（114±5 μU/ml）达到了相当的血浆胰岛素水平。然而，糖尿病患者的葡萄糖输注速率（4.7±0.4 mg/kg·min）比对照组低30%（P<0.01）。在糖尿病患者中，葡萄糖输注速率与空腹血浆葡萄糖水平直接相关（r = 0.57，P<0.05）。在5名糖尿病患者中，葡萄糖代谢与对照组相似，且这些糖尿病患者的空腹血糖水平最高。当他们在空腹血浆葡萄糖先前经胰岛素正常化（至100±1 mg/dl）后再次接受研究时，胰岛素钳夹期间的葡萄糖输注速率比高血糖时观察到的低30%（P<0.01）。采用氚标记葡萄糖测量内源性葡萄糖生成的研究表明，在糖尿病患者和对照者的高胰岛素血症期间，肝脏葡萄糖生成受到类似的90 - 95%的抑制。糖尿病患者中（125）I - 胰岛素与单核细胞的结合（5.5±0.6%）比对照组低30%（P<0.01）。在对照组（r = 0.67，P<0.01）和糖尿病患者（r = 0.88，P<0.001）中，胰岛素与单核细胞的结合以及用胰岛素钳夹测定的胰岛素作用高度相关。我们得出结论：（a）大多数成年发病型糖尿病患者对生理性高胰岛素血症的组织敏感性降低；（b）这种敏感性降低至少部分位于肝外组织；（c）对胰岛素的抵抗可能由胰岛素结合减少介导；（d）在对胰岛素具有正常组织敏感性的成年发病型糖尿病患者中，高血糖可能是胰岛素介导的葡萄糖摄取正常速率的一个促成因素。
