SUBSTRATE REGULATION BY RHIGF-1 IN OBESITY AND AGING

外周胰岛素敏感性降低是许多葡萄糖的共同特征 包括衰老和肥胖在内的不容忍状态。胰岛素剂量-反应 葡萄糖利用、肝脏葡萄糖产生和全身的曲线 肥胖症和衰老的蛋白质周转率已经确定。 胰岛素样生长因子I(IGF-I)，一种主要由 肝脏具有类似于胰岛素和生长激素的特性。 然而，与胰岛素不同的是，IGF-I不会刺激脂肪沉积。与 重组人IGF-I的可用性，有可能表征 上述代谢参数在葡萄糖中的剂量-反应曲线 无法忍受的衰老状态。拟议的研究将采用 胰岛素或重组人胰岛素样生长因子-I输注的正血糖钳夹技术氚 还将使用葡萄糖和13C-亮氨酸方法学来定量 葡萄糖和蛋白质周转。将对患者进行肌肉活组织检查 GLUT-4转运蛋白的测量。这些研究将有助于阐明 胰岛素样生长因子-I对血糖和蛋白质稳态的影响。该机制的目的是 葡萄糖利用率的预期增加被认为是通过 葡萄糖转运蛋白的增加，这将在两个方面进行评估 衰老与肥胖模型。这些研究将提供有价值的基础数据 在形成治疗糖耐量异常状态的指南方面 肥胖、衰老和糖尿病的风险。

Reduced peripheral insulin sensitivity is a common feature of many glucose intolerant states including aging and obesity. Insulin dose-response curves for glucose utilization, hepatic glucose production and total body protein turnover rates have been established for both obesity and aging. Insulin-like growth factor I (IGF-I), a hormone produced predominately from the liver, has properties similar to insulin as well as to growth hormone. However, unlike insulin, IGF-I does not stimulate fat deposition. With the availability of recombinant human IGF-I, it is possible to characterize the dose-response curve for the metabolic parameters described above in glucose intolerant states of aging. The proposed studies will employ the euglycemic clamp technique with infusion of insulin or rhIGF-I. Tritiated glucose and 13C-leucine methodology will also be employed to quantitate glucose and protein turnover. Muscle biopsies will be obtained for the measurement of Glut-4 transporters. These studies will help elucidate the efficacy of IGF-I on glucose and protein homeostasis. The mechanism for the expected increase in glucose utilization is thought to be via an increase in glucose transporters and this will be evaluated in both the aging and obesity model. These studies will contribute basic data valuable in the formation of guidelines for therapy in the glucose intolerant states of obesity, aging and diabetes.