ROLE OF FREE FATTY-ACIDS IN INSULIN-RESIS TANCE OF SUBJECTS WITH NON-INSULIN-DEPENDENT DIABETES

Non-insulin-dependent diabetes (NIDDM) is characterized by overproduct ion of glucose, decreased effects of insulin on glucose utilization an d production, and a defect in glucose-induced insulin secretion. NIDDM is also associated with defects in fatty acid metabolism, i.e. enhanc ed lipolysis and impaired suppression of adipose tissue lipolysis in r esponse to insulin, and increased plasma free fatty acid levels. It ha s been suggested that the ''glucose-fatty acid cycle'' is enhanced in NIDDM and could contribute to disturbed glucose homeostasis. Although the use of intralipid + heparin infusion and inhibitors of lipolysis o r fatty acid oxidation indicates that the glucose-fatty acid cycle exi sts both in normal and NIDDM subjects, it does not seem to be the prim ary cause of disturbed glucose homeostasis in lean NIDDM subjects or t heir first-degree relatives. However, the glucose-fatty acid cycle cou ld contribute to overproduction of glucose (by stimulating gluconeogen esis) and muscle insulin resistance in obese NIDDM subjects. Studies p erformed in the rat suggest that impaired glucose-induced insulin secr etion could also be related to chronic exposure of pancreatic beta cel ls to elevated plasma free fatty acid levels. The role of the glucose- fatty acid cycle in normal subject must be clarified, and its contribu tion to decreased glucose-induced insulin secretion in NIDDM requires further investigation.