Glucose-induced insulin hypersecretion in lipid-infused healthy subjects is associated with a decrease in plasma norepinephrine concentration and urinary excretion

We investigated the effect of a 48 h triglyceride infusion on the subsequen t insulin secretion in response to glucose in healthy men. We measured the variations in plasma concentration and urinary excretion of catecholamines as an indirect estimation of sympathetic tone. For 48 h, 20 volunteers rece ived a triglyceride/heparin or a saline solution, separated by a 1-month in terval. At time 48 h, insulin secretion in response to glucose was investig ated by a single iv glucose injection (0.5 g/kg(-1)) followed by an hypergl ycemic clamp (10 mg.kg(-1).min(-1), during 50 min). The triglyceride infusi on resulted in a 3-fold elevation in plasma free fatty acids and an increas e in insulin and C-peptide plasma concentrations (1.5- and 2.5-fold, respec tively, P < 0.05), compared with saline. At time 48 h of lipid infusion, pl asma norepinephrine (NE) concentration and urinary excretion levels were lo wered compared with saline (plasma NE: 0.65 +/- 0.08 vs. 0.42 +/- 0.06 ng/m l, P < 0.05; urinary excretion: 800 +/- 70 vs. 620 +/- 25 nmol/24 h, P < 0. 05). In response to glucose loading, insulin and C-peptide plasma concentra tions were higher in lipid compared with saline infusion (plasma insulin: 6 00 +/- 98 vs. 310 +/- 45 pM, P < 0.05; plasma C-peptide 3.5 +/- 0.2 vs. 1.7 +/- 0.2 nM, P < 0.05). In conclusion, in healthy subjects, a 48-h lipid in fusion induces basal hyperinsulinemia and exaggerated insulin secretion in response to glucose which may be partly related to a decrease in sympatheti c tone.