The objective of this project is to investigate the mechanism(s) responsible for the changes in glucose uptake into muscle in response to exercise and diabetes. Like insulin, muscular contraction increases the rate of glucose transport into muscle. Endurance exercise training increases both the sensitivity and responsiveness of muscle to insulin. In contrast to exercise training, diabetic patients exhibit decreased overall glucose utilization, and particularly decreased glucose utilization by peripheral tissue (muscle). The intriguing question arising from these findings is: Does endurance exercise training alleviate the post receptor defect in glucose uptake that is characteristic of diabetes? Our working hypothesis is that the total number of glucose transporters in muscle is increased by endurance exercise training and decreased by diabetes and that muscular contraction increases glucose uptake into muscle by causing the translocation of glucose transporters to the plasma membrane. We will first determine the effects of exercise and diabetes on glucose transport into muscle using both intact animals (rats) and perfused muscle preparations. After we establish the effects of exercise and diabetes on glucose transport, we will then proceed to investigate the changes in number, membrane distribution, structure, and function of the glucose transporter. To investigate our hypothesis we will seek answers to the following questions: 1) Does training increase the total number of glucose transporters in muscle? 2) Is the number of glucose transporters decreased in muscle of diabetics and can this defect be ameliorated by endurance exercise? 3) Does muscle contraction cause the translocation of glucose transporters from the """"""""microsomal"""""""" measures to the plasma membrane? 4) Are there changes in the structure and/or function of the glucose transporter as a result of exercise or diabetes? 5) Are changes in the number of glucose transporters a result of altered transporter mRNA levels? Our previous experience with the exercising rat model and perfused hindquarter preparations, along with our recently developed methods for isolating plasma and microsomal membranes give us an opportunity to study a significant question that will provide fundamental information about the mechanism responsible for the hyperglycemia of diabetes and whether the defect can be ameliorated by exercise training.
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