PATHOGENESIS OF DIABETES MELLITUS

胰岛素抵抗，一种高度流行的状态，影响约50% 在人群中，是负责一些病理生理的 病症包括II型糖尿病。胰岛素的主要部位 用传统方法测定的阻力是肌肉。的作用 可能影响肌肉胰岛素敏感性的三个因素是 探索性--内在肌纤维轮廓(I、IIa和IIb类型)、肌肉 膜流动性及其决定因素(如磷脂脂肪酸 成分)和胰岛素诱导的肌肉血流量增加。 固有的肌肉纤维特征可能在 胰岛素抵抗和基础能量消耗的改变将被检查。 将测定受试者的胰岛素敏感性和能量消耗。 从肌肉纤维组成的上、下五分位数(下 五分之一=I型纤维减少；IIb纤维增加)。研究是设计的 以确定在胰岛素中观察到的肌肉纤维轮廓是否发生变化 阻力是主要的还是次要的，以及哪种纤维类型的组成是 更容易发生可诱导的胰岛素抵抗。 此外，这些研究还将探索环境因素(饮食 和运动)影响膜流动性和肌肉磷脂脂肪 感兴趣的酸成分与固有的肌肉轮廓产生 胰岛素敏感性的变化。同卵双胞胎 II型糖尿病的不和谐将被用来探测相互作用 遗传因素和环境因素对肌肉的影响 在确定胰岛素敏感性方面具有公认的重要特征。 最后，将检验这一假设，即肥胖和肥胖的FFA增加 胰岛素抵抗状态可能会削弱正常的血流动力学反应 胰岛素通过抑制中枢介导的肾上腺素能反应，从而 导致肌肉的胰岛素抵抗。

Insulin resistance, a highly prevalent state affecting approximately 50% of the population, is responsible for a number of pathophysiologic conditions including type II diabetes. The major site of insulin resistance as determined by conventional methods is muscle. The role of three factors likely to influence muscle insulin sensitivity will be explored--intrinsic muscle fiber profile (type I, IIa, and IIb), muscle membrane fluidity and its determinants (e.g., phospholipid fatty acid composition) and insulin-induced augmentation of muscle blood flow. The possibility that inherent muscle fiber profile may play a role in insulin resistance and altered basal energy expenditure will be examined. Insulin sensitivity and energy expenditure will be determined in subjects from the upper and lower quintiles for muscle fiber composition (lower quintile = decreased type I; increased IIb fibers). Studies are designed to determine whether muscle fiber profile changes observed in insulin resistance are primary or secondary, and which fiber type composition is more susceptible to inducible insulin resistance. Additionally these studies will explore how environmental factors (diet and exercise) affecting membrane fluidity and muscle phospholipid fatty acid composition interest with the inherent muscle profile to produce changes in insulin sensitivity. Monozygotic twins concordant and discordant for Type II diabetes will be used to probe the interaction between genetic and environmental factors in influencing muscle characteristics putatively important in determining insulin sensitivity. Finally the hypothesis will be examined that increased FFA of obesity and insulin resistant states may blunt the normal hemodynamic response to insulin by suppression of centrally-mediated adrenergic responses, thereby contributing to insulin resistance of muscle.