Youngren J F, Goldfine I D, Pratley R E
Department of Medicine, Mount Zion Medical Center, University of California, San Francisco 94143-1616, USA.
Am J Physiol. 1997 Aug;273(2 Pt 1):E276-83. doi: 10.1152/ajpendo.1997.273.2.E276.
Defects in insulin receptor tyrosine kinase activity are present in insulin-resistant non-insulin-dependent diabetes mellitus patients and certain nondiabetic individuals, both lean and obese. However, the relationship between insulin receptor function, insulin action, and obesity is unclear. To address this issue, we have employed a new and highly sensitive enzyme-linked immunosorbent assay to measure in vitro insulin-stimulated autophosphorylation of immunocaptured muscle insulin receptors in a group of 25 normoglycemic Pima Indians. Insulin action, determined during two-step euglycemic insulin clamps, varied widely in these subjects. Maximal in vitro insulin stimulation of insulin receptor autophosphorylation strongly correlated with both low (Mlow)- and high (Mhigh)-dose insulin-stimulated glucose disposal (r = 0.62 and 0.51, P < 0.002 and 0.011, respectively). Insulin receptor autophosphorylation was inversely related to percent body fat (r = -0.52, P < 0.009). After control for percent body fat, receptor autophosphorylation remained correlated with Mlow (partial r = 0.49, P < 0.025). These data therefore suggest that defects in insulin receptor function are major contributors to insulin resistance in both lean and obese normoglycemic Pima Indians.
胰岛素抵抗的非胰岛素依赖型糖尿病患者以及某些非糖尿病个体（包括瘦人和肥胖者）体内存在胰岛素受体酪氨酸激酶活性缺陷。然而，胰岛素受体功能、胰岛素作用与肥胖之间的关系尚不清楚。为了解决这个问题，我们采用了一种新型高灵敏度酶联免疫吸附测定法，来检测一组25名血糖正常的皮马印第安人免疫捕获的肌肉胰岛素受体在体外胰岛素刺激下的自身磷酸化情况。在两步正常血糖胰岛素钳夹过程中测定的胰岛素作用，在这些受试者中差异很大。体外胰岛素对胰岛素受体自身磷酸化的最大刺激作用与低剂量（Mlow）和高剂量（Mhigh）胰岛素刺激的葡萄糖处置均密切相关（r分别为0.62和0.51，P < 0.002和0.011）。胰岛素受体自身磷酸化与体脂百分比呈负相关（r = -0.52，P < 0.009）。在控制体脂百分比后，受体自身磷酸化仍与Mlow相关（偏r = 0.49，P < 0.025）。因此，这些数据表明，胰岛素受体功能缺陷是瘦人和肥胖血糖正常的皮马印第安人胰岛素抵抗的主要原因。
