Lack of effect of a physiological elevation of plasma non-esterified fattyacid levels on insulin secretion

Elevated plasma non-esterified fatty acid (NEFA) levels in obese subjects m ay contribute to their higher insulin secretory rates by direct effects on the islet beta-cells. This may involve short-term metabolic effects, or lon g-term effects on islet (beta-cell mass, which is characteristically increa sed in obesity. We examined the effects of elevating plasma NEFA levels for 5.5 to 7 h on insulin secretion after an overnight fast and during a 90 mi n 12 mmol/l hyperglycemic clamp in 9 normal women (40.1 +/- 9.5 years [mean +/- SD]; BMI: 25.2 +/- 3.72 kg/m(2)). Subjects were studied twice. In one study plasma NEFA levels were increased approximately 2-fold by infusion of 20% Intralipid (60 ml/h) and heparin (900 U/h) for 5.5 h before and throug hout the glucose clamp. Elevated NEFA levels were associated with a small i ncrease in fasting plasma glucose (5.0 +/- 0.1 vs 4.7 +/- 0.1 mmol/l, P < 0 .05) and C-peptide levels (0.54 +/- 0.09 vs 0.41 +/- 0.06 nmol/l, P < 0.05) . The increase in fasting insulin levels did not, however, reach statistica l significance (9.0 +/- 2.5 vs 5.3 +/- 1.4 mU/l, NS). During the glucose da mp, plasma NEFA levels were suppressed to very low levels in the saline con trol study. Although plasma NEFA levels also fell in the lipid/heparin stud y, they remained significantly higher than on the control day, and somewhat higher than might be expected postprandially in obese subjects. During the glucose clamps, plasma glucose, insulin, and C-peptide profiles were simil ar on the two study days. No difference in either first or second phase ins ulin secretion was observed between the two studies. In conclusion, our fin dings do not support the idea that the exaggerated insulin secretion in obe sity is mediated by short-term effects of plasma NEFA levels on islet beta- cell metabolism, independent of plasma glucose levels.