Thompson D B, Pratley R, Ossowski V
Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
J Clin Invest. 1996 Nov 15;98(10):2346-50. doi: 10.1172/JCI119046.
Insulin resistance is a predictor of the development of noninsulin-dependent diabetes mellitus (NIDDM) in humans. It is unclear whether insulin resistance is a primary defect leading to NIDDM or the result of hyperinsulinemia and hyperglycemia. To determine if insulin resistance is the result of extrinsic factors such as hyperinsulinemia primary skeletal muscle cell cultures were established from muscle biopsies from Pima Indians with differing in vivo insulin sensitivities. These cell cultures expressed a variety of muscle-specific phenotypes including the proteins alpha-actinin and myosin, muscle-specific creatine kinase activity, and RNA encoding GLUT4, MYF5, MYOD1, and MYOGENIN. Labeled glucose was used to measure the insulin-stimulated conversion of glucose to glycogen in these cultures. The in vivo rates of insulin-stimulated glycogen production (insulin resistance) were correlated with in vitro measures of glycogen production (P = 0.007, r = 0.58). This defect in insulin action is stable in a uniform culture environment and is retained over time. The retention of insulin resistance in myoblast derived cell cultures is consistent with the expression of an underlying biochemical defect in insulin resistant skeletal muscle.
胰岛素抵抗是人类非胰岛素依赖型糖尿病（NIDDM）发生发展的一个预测指标。目前尚不清楚胰岛素抵抗是导致NIDDM的原发性缺陷，还是高胰岛素血症和高血糖的结果。为了确定胰岛素抵抗是否是诸如高胰岛素血症等外在因素的结果，从体内胰岛素敏感性不同的皮马印第安人的肌肉活检样本中建立了原代骨骼肌细胞培养物。这些细胞培养物表达了多种肌肉特异性表型，包括α-辅肌动蛋白和肌球蛋白等蛋白质、肌肉特异性肌酸激酶活性，以及编码葡萄糖转运蛋白4（GLUT4）、肌原性决定因子5（MYF5）、肌源性分化抗原1（MYOD1）和生肌调节因子（MYOGENIN）的RNA。使用标记葡萄糖来测量这些培养物中胰岛素刺激的葡萄糖向糖原的转化。体内胰岛素刺激的糖原生成率（胰岛素抵抗）与体外糖原生成测量值相关（P = 0.007，r = 0.58）。胰岛素作用的这一缺陷在统一的培养环境中是稳定的，并且会随时间持续存在。成肌细胞衍生的细胞培养物中胰岛素抵抗的持续存在与胰岛素抵抗性骨骼肌中潜在生化缺陷的表达一致。
