PATHOGENESIS OF DIABETES MELLITUS

胰岛素抵抗是一种非常普遍的状态，影响约50%的 的人口，是负责一些病理生理 包括II型糖尿病。 胰岛素的主要作用部位 通过常规方法测定的电阻是肌肉。 的作用 可能影响肌肉胰岛素敏感性的三个因素是 探索-内在肌纤维轮廓（I型，IIa型和IIb型），肌肉 膜流动性及其决定因素（例如，磷脂脂肪酸 组合物）和胰岛素诱导的肌肉血流量增加。 固有的肌纤维轮廓可能在 将检查胰岛素抵抗和改变的基础能量消耗。 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五分位数和下五分位数（下五分位数）， 五分位数= I型纤维减少; IIb型纤维增加）。 研究设计 以确定在胰岛素中观察到的肌纤维分布变化是否 阻力是主要的还是次要的， 更容易出现诱导型胰岛素抵抗。 此外，这些研究还将探讨环境因素（饮食） 影响膜流动性和肌磷脂脂肪 酸组合物的利益与固有的肌肉轮廓，以产生 胰岛素敏感性的变化。 单卵双胞胎一致， II型糖尿病的不一致性将用于探索相互作用 遗传和环境因素对肌肉的影响 这些特征在决定胰岛素敏感性方面非常重要。 最后，将检验肥胖和肥胖症患者FFA增加的假设， 胰岛素抵抗状态可能会减弱正常的血液动力学反应， 通过抑制中枢介导的肾上腺素能反应， 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.