NEFA ELEVATION DURING A HYPERGLYCEMIC CLAMP ENHANCES INSULIN-SECRETION

Elevated non-esterified fatty acid (NEFA) levels may influence insulin secretion and contribute to the development of Type 2 DM. We investig ated the effects of acute NEFA elevation in controls (n=6) and subject s predisposed to Type 2 DM (n=6) on basal insulin levels, and followin g glucose and arginine stimulation. Each subject had one study with a triglyceride (TG) plus heparin infusion (elevated NEFA levels) and ano ther with normal saline. Twenty minutes after the TG or saline infusio n began a glucose bolus was given and 10 min later a 90-min hyperglyca emic clamp (similar to 9 mmol l(-1)) was started. Intravenous arginine was given at 110 min. Elevated NEFA levels (similar to 4000 mu mol l( -1)) did not enhance basal or first phase glucose stimulated insulin l evels. During hyperglycaemia, NEFA elevation further increased insulin levels in both groups by 20-44 % (p < 0.05) and C-peptide levels by 1 7-25 % (p < 0.05). The post-arginine insulin levels during hyperglycae mia were increased by 45 % in the Type 2 DM-risk group (p < 0.02). The glucose infusion rate maintaining matched hyperglycaemia was similar during NEFA elevation and for saline control for both groups. We concl ude that acute elevation of NEFA levels enhances glucose and non-gluco se-induced insulin secretion. (C) 1998 John Wiley & Sons, Ltd.