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.
