BODY FAT DISTRIBUTION AND METABOLIC PROFILE IN WOMEN

腹部内脏脂肪模式已成为一个重要的预测指标 糖耐量异常、血脂异常、高血压和他们的 心血管并发症。它也是一种独特的模式 NIDDM的糖尿病前期状态。导致不利因素的主要途径 代谢谱与胰岛素抵抗和胰岛素抵抗的共存有关 内脏胰岛素动力学中的适应性。这个项目的总体目标是 该项目将继续寻找，以确定哪些基本机制 促进胰岛素抵抗和内脏适应 腹型肥胖与非胰岛素依赖型糖尿病易感性的胰岛素动态研究 三个全球具体目标和六个假设构成了这一新的 指令。 特定目标1：确定胰岛素介导的毛细血管调节 血流灌注及其与糖代谢和胰岛素的关系 腹型肥胖的抵抗力。 假设一：胰岛素作用的一个限速步骤是它的能力 诱导骨骼肌毛细血管血流的重新分布和 从而影响参与葡萄糖摄取的细胞团和 它的新陈代谢通道。假设1.2：钝化胰岛素诱导 毛细管流重新分布，可能是由于α- 肾上腺素能血管反应性紧张导致糖代谢受损 以及腹型肥胖的胰岛素抵抗。 具体目标2：评估腹型肥胖与 内脏FFA流量与肝脏胰岛素提取。 假设2.1：腹型肥胖患者内脏FFA流量增加 由于内脏FFA释放的抑制作用减弱。 假设2.2：肝脏胰岛素提取，从而导致全身性 胰岛素流量受肝脏FFA暴露水平的调节。 具体目标3：确定胰岛素的分泌、搏动和反应 动力学及其与腹型肥胖及其相关因素的关系 NIDDM的易感性。 假设3.1：腹型肥胖患者的胰岛素需求增加 通过增加胰岛素产量和分泌性脉动来补偿 具有正常的周期和增大的脉冲幅度。 假设3.2：在遗传倾向的个体中，额外的 β细胞分泌的缺陷使分泌的中断永久化 脉搏和胰岛素产量的相对下降。 使用最先进的技术和全面的临床研究来 实现这些目标，了解潜在的生物机制 腹部不良代谢与NIDDM易感性的关系 肥胖女性很可能会进化。

Abdominal visceral fat patterning has emerged as an important predictor of glucose intolerance, dyslipoproteinemia, hypertension, and their cardiovascular complications. It is also a unique model of the prediabetic state for NIDDM. The major pathways leading to the adverse metabolic profile are linked by the coexistance of insulin resistance and adaptations in splanchnic insulin dynamics. The overall goals of this project is to continue to search to identify fundamental mechanisms which contribute to the insulin resistance and to the adaptations of splanchnic insulin dynamics in abdominal obesity and their predisposition to NIDDM. Three global specific aims and six hypotheses form the basis for this new directive. Specific Aim 1: Determine insulin-mediated regulation of capillary perfusion and its relationship to glucose metabolism and the insulin resistance of abdominal obesity. Hypothesis I.I: A rate-limiting step in insulin action is its ability to induce the redistribution of capillary flow in skeletal muscle and consequently influence the cellular mass engaged in glucose uptake and its metabolic channelling. Hypothesis 1.2: Blunted insulin-induced capillary flow redistribution, presumably due to increased alpha- adrenergic vasoreactive tone, contributes to impaired glucose metabolism and to the insulin resistance of abdominal obesity. Specific Aim 2: Evaluate the relationship of abdominal obesity with splanchnic FFA flux and hepatic insulin extraction. Hypothesis 2.1: In abdominal obesity, splanchnic FFA flux is increased as a result of diminished suppressibility of splanchnic FFA release. Hypothesis 2.2: Hepatic insulin extraction and consequently the systemic flow of insulin are regulated by the level of hepatic FFA exposure. Specific Aim 3: Determine insulin secretion pulsitilities and response dynamics and their relationships with abdominal obesity and its predisposition to NIDDM. Hypothesis 3.1: Increased insulin demand in abdominal obesity is compensated by increased insulin production, with secretory pulsitilities of normal periodicities and increased pulse amplitudes. Hypothesis 3.2: In genetically predisposed individuals, an additional defect in beta cell secretion perpetuates disruption of the secretory pulsitilities and the relative decline in insulin production. State of art techniques and thorough clinical investigations are used to fulfill these goals, Understanding of biologic mechanisms underlying the adverse metabolic profile and predisposition to NIDDM in abdominally obese women is likely to evolve.