There are an estimated 11 million diabetic patients in this country and approximately 80 percent are classified as Type II or non-insulin-dependent. Glucose intolerance is well recognized in both Type I and Type II diabetic patients, and has been attributed to both receptor and post-receptor defects. Since glucose intolerance is a major risk factor for the development of atherosclerosis our understanding of the mechanism involved and ways of reducing or reversing glucose intolerance is important for the health of this nation. The purpose of this proposal is to better understand the mechanisms involved in glucose transport in skeletal muscle and the roles played by both exercise and diet in regulating glucose transport. Previous studies have used nontarget tissues such as red blood cells or monocytes to evaluate changes in affinity and number of insulin receptors. Our initial data indicated that changes in these nontarget tissues do not refect changes in skeletal muscle insulin receptors following exercise training. Our studies are designed to test the effects of regular exercise and a low-fat diet on glucose tolerance, insulin binding to skeletal muscle sarcolemma (SL) membranes, and specific D-glucose transport by the sarcolemma vesicles. The total number and affinity of SL functional glucose transport units will be assessed by determining the D-glucose inhibitable class of cytochalasin B binding sites. We will also assess the ability of insulin to translocate the glucose transport units from the interior of the cell into the SL membrane. These studies will be done on normal rats as well as rats made diabetic by stroptozotocin treatment. The results should enhance our understanding of glucose transport in normal and diabetic muscle, separate differences between receptor and post-receptor defects and provide a scientific basis for the use of regular exercise and a low-fat diet by both Type I and Type II diabetic patients.
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