EFFECT OF AGE ON PANCREATIC BETA CELL RESPONSE TO CHANGES IN INSULIN SENSITIVITY

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As diabetes develops in a significant proportion of the aging population, changes of glucose metabolism occurring with aging may play an important role in the development of this disease. The objective of this project is to study age differences in regulation of glucose metabolism in people. Insulin is a hormone, made by special cells of the pancreas called beta cells, which is a key regulator of glucose. We hypothesize that subtle differences in insulin secretion and adaptation to changes in the body's response to insulin will distinguish these groups and provide insight about the effect aging has on these processes. Three groups of individuals will be studied: 1) healthy elderly with no abnormality of glucose tolerance, 2) healthy elderly with glucose intolerance and 3) healthy young subjects. Initial screening determines eligibility to participate in the study. If eligible to participate, a subject will have an initial intravenous glucose tolerance test (IVGTT) to determine the body's sensitivity to insulin. After the initial IVGTT, the subject takes either a similar appearing but inactive capsule (placebo) or nicotinic acid for two weeks. Nicotinic acid is used by physicians to treat people with high blood fat levels. It also causes a temporary decrease in insulin sensitivity, which will return to normal after the medication is stopped. At the end of this period, the subjects have another IVGTT on one day and a glucose ramp (a procedure designed to measure insulin secretion) on the following day. The order of drug/placebo is determined randomly. Medication is given in a double-blind crossover manner which means neither the subject nor the investigator knows whether nicotinic acid or the placebo capsule is being administered and that each subject will have both drug and placebo during the study. Following at least a washout period of at least two weeks, the above procedure is repeated with the other drug/placebo. By experimentally inducing a decline of sensitivity to insulin using pharmacological methods we will observe the impact of experimentally induced insulin resistance on pancreatic beta cell function in these three groups.