Häring H
Institut für Diabetesforschung München.
Herz. 1995 Feb;20(1):5-15.
Insulin resistance of skeletal muscle, liver and fat combined with an abnormality of insulin secretion characterizes Type 2 (non-insulin-dependent) diabetes mellitus. There is increasing evidence that the insulin resistance of the skeletal muscle plays a key role early in the development of Type 2 diabetes. As a consequence recent research efforts have focussed on the characterization of insulin signal transduction elements in the muscle which are candidates for a localization of a defect causing insulin resistance, i.e. the insulin receptor, phosphatases related to insulin action, glycogen synthase and the glucose transporters. In this review we attempt to summarize present knowledge about abnormalities of these systems in skeletal muscle of Type 2 diabetic and pre-diabetic individuals. We try to classify abnormalities as secondary events or as candidates for putative primary molecular defects which might initiate the development of insulin resistance as early as in the "pre-diabetic" state. Insulin resistance is combined with abnormalities of insulin secretion. Compensatory hypersecretion of insulin is typically found in early stages of the development of the "Metabolic Endocrine Syndrome" and the pre-diabetic state. The transition from this pre-diabetic state to the clinically overt Type 2 diabetes is accompanied or even caused by declining insulin secretion. The molecular mechanism causing declining insulin secretion is not understood in detail. Beside genetically determined factors regulatory events might be important.
骨骼肌、肝脏和脂肪的胰岛素抵抗，再加上胰岛素分泌异常，是2型（非胰岛素依赖型）糖尿病的特征。越来越多的证据表明，骨骼肌的胰岛素抵抗在2型糖尿病的早期发展中起关键作用。因此，最近的研究工作集中在肌肉中胰岛素信号转导元件的特征描述上，这些元件是导致胰岛素抵抗缺陷定位的候选因素，即胰岛素受体、与胰岛素作用相关的磷酸酶、糖原合酶和葡萄糖转运蛋白。在这篇综述中，我们试图总结目前关于2型糖尿病患者和糖尿病前期个体骨骼肌中这些系统异常的知识。我们试图将异常分类为继发事件或可能在“糖尿病前期”状态就引发胰岛素抵抗发展的假定原发性分子缺陷的候选因素。胰岛素抵抗与胰岛素分泌异常相关。在“代谢内分泌综合征”和糖尿病前期状态的早期发展阶段，通常会出现胰岛素的代偿性高分泌。从这种糖尿病前期状态转变为临床显性2型糖尿病伴随着甚至是由胰岛素分泌下降引起的。导致胰岛素分泌下降的分子机制尚不清楚。除了遗传决定的因素外，调节事件可能也很重要。
