LIPID INTERACTIONS WITH INSULIN SECRETION AND INSULIN SENSITIVITY

The purpose of this study is to better understand the relationship between lipid metabolism, insulin secretion and insulin resistance. Animal studies suggest that free fatty acids are essential for normal insulin secretory dynamics. Abnormally increased availability of free fatty acids may lead to hyperinsulinemia or impaired glucose stimulated insulin secretion (hyperglycemia-NIDDM). Excessive availability of free fatty acids for oxidation may impair insulin stimulated glucose oxidation and storage body wide (insulin resistance). This excess FFA supply can arise from the plasma pool or reside within the muscle tissue itself. This study is aimed at studying normal and abnormal insulin secretory dynamics, the relationship to insulin resistance, Non-insulin dependent diabetes and excess availability of FFA.Four groups of individuals with a variety of degrees of insulin resistance, hyperglycemia and increased availability of FFA are chosen. All subjects will be subject to an intravenous glucose tolerance test with and without nicotinic acid to suppress lipolysis and thus decrease FFA levels. The insulin secretory response will be monitored and its relationship to available FFA analyzed. In addition, hyperinsulinemic glucose clamps will be done to measure insulin sensitivity. As part of the clamp, porcine insulin will be infused to calculate insulin clearance rates.