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 葡萄糖耐受不良、血脂异常、高血压及其 心血管并发症 它也是一个独特的模式， NIDDM的前驱状态。 导致不良反应的主要途径 代谢谱与胰岛素抵抗的共存有关， 内脏胰岛素动力学的适应。 本项目的总体目标 项目的目的是继续寻找基本机制， 有助于胰岛素抵抗和内脏器官的适应， 腹型肥胖者胰岛素动力学及其对NIDDM易感性的影响 三个全球具体目标和六个假设构成了这一新目标的基础。 指令。 具体目标1：确定胰岛素介导的毛细血管调节 灌注及其与葡萄糖代谢和胰岛素的关系 抵抗腹部肥胖。 假设I.I：胰岛素作用的限速步骤是它的能力 诱导骨骼肌中毛细血管流量的重新分布， 从而影响参与葡萄糖摄取的细胞质量， 它的代谢通道 假设1.2：胰岛素诱导的钝化 毛细血管流量重新分布，可能是由于增加的α- 肾上腺素能血管反应性紧张，导致糖代谢受损 以及腹部肥胖的胰岛素抵抗。 具体目标2：评价腹型肥胖与 内脏FFA通量和肝脏胰岛素提取。 假设2.1：在腹型肥胖中，内脏FFA通量增加 这是由于内脏FFA释放的抑制性降低。 假设2.2：肝脏胰岛素提取和因此全身胰岛素分泌 胰岛素的流量受肝脏FFA暴露水平的调节。 具体目标3：确定胰岛素分泌脉动性和反应 动力学及其与腹型肥胖及其 易患NIDDM。 假设3.1：腹型肥胖者胰岛素需求增加， 通过增加胰岛素产生来补偿，伴有分泌脉动 正常的周期性和增加的脉冲幅度。 假设3.2：在有遗传倾向的个体中， β细胞分泌的缺陷使分泌的破坏永久化， 脉动性和胰岛素产生的相对下降。 最先进的技术和全面的临床研究用于 实现这些目标，了解潜在的生物学机制， 腹型糖尿病患者的不良代谢特征和NIDDM易感性 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.