ACUTE LOWERING OF PLASMA FATTY-ACIDS LOWERS BASAL INSULIN-SECRETION IN DIABETIC AND NONDIABETIC SUBJECTS

The objective of this study was to determine whether basal plasma free fatty acid (FFA) concentrations affect basal insulin secretion rates (ISRs). Effects of FFA levels on basal ISRs were evaluated by lowering basal plasma FFA levels with nicotinic acid (NA) (100-150 mg p.o., q 30 min X 4 h) in type 2 diabetic patients and in normal volunteers. Lo wering of FFAs (from similar to 600 to similar to 100 mu mol/l) lowere d ISRs in type 2 diabetic patients during isoglycemic clamping (from 1 39 to 101 pmol/min; -23%; P < 0.02) and euglycemic clamping (from 99 t o 63 pmol/min; -36%; P < 0.03) and in normal subjects during euglycemi c clamping (from 127 to 96 pmol/min; -25%; P < 0.03). In addition, per ipheral insulin concentrations decreased by similar to 30% in diabetic and nondiabetic subjects. NA had no direct effect on ISRs; that is, N A did not change ISRs when plasma FFAs were prevented from decreasing with a lipid/heparin infusion, mie concluded that 1) basal plasma FFAs exerted physiologically important, longlasting effects supporting 25- 33% of basal insulin secretion in nondiabetic and diabetic subjects; 2 ) basal plasma FFAs were responsible for some of the hyperinsulinemia in normoglycemic obese subjects; and 3) NA had no direct effect on ins ulin secretion.