GLP-1 EFFECTS ON INSULIN SECRETION AND SENSITIVITY IN TYPE II DIABETES

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Glucagon-like peptide-1 (GLP-1) is a naturally produced peptide hormone which is secreted from the jejunum and ilium following food intake. It is the most potent insulinotropic agent in humans, i.e., it synergizes with glucose to augment insulin secretion. In contrast to the effects of incretins in glucose tolerant states, GLP-1 has been shown to be insulinotropic in Type II diabetic subjects, unlike the other well-known incretin, glucose-dependent insulinotropic peptide (GIP). In addition, several studies have implicated an independent role for GLP-1 similar to that of insulin, i.e., the ability to enhance glucose uptake independent of its insulinotropic effect. Thus GLP-1 has the potential to be a therapeutic agent in Type II diabetic states. We will deliver GLP-1 subcutaneously to Type II diabetic subjects for 48 hours, checking insulin secretion and sensitivity, before and after the infusions, in response to glucose delivered by way of clamp technology We previously performed a short (one hour) infusion of GLP-1 intraveneously and were not able to demonstrate extrapancreatic effects. A longer infusion should decisively demonstrate whether there are in fact any extrapancreatic effects of the GLP-1. CORE LABORATORY ONLY; NO INPATIENT DAYS OR OUTPATIENT VISITS.