Dose-response characteristics for glucose-stimulated insulin release in man and assessment of influence of glucose on arginine-stimulated insulin release

Abstract

Glucose potentiates arginine-induced insulin release. We investigated the dose-response characteristics for both phases of glucose-induced insulin release in normal man, and studied the influence of hyperglycemia on arginine-induced insulin secretion. Dose-response curves of plasma C-peptide increments achieved during 60-minute hyperglycemia clamps (7, 11, 17, 24, and 32 mmol/L) with and without a primed continuous infusion of arginine (infusion rate, 15 mg/kg/min) were analyzed with a modified Michaelis-Menten equation. The ED 50 (half-maximally stimulating blood glucose concentration) of first-phase insulin release (determined from plasma C-peptide increments at 5 minutes) was significantly lower than the ED 50 for the second phase (60 minutes; 8.4 ± 0.8 v 14.3 ± 1.3 mmol/L, respectively, P < .002). Combined glucose-arginine stimulation significantly increased insulin release. Vmax of both phases of glucose-arginine-stimulated insulin release were positively correlated ( r = .75, P < .05). The ED 50 of the influence of glucose on first-phase arginine-induced insulin release was significantly lower than the ED 50 for the second phase (9.0 ± 1.1 v 12.7 ± 1.0 mmol/L, respectively, P < .02). For each insulin secretion phase separately, the ED 50 for the influence of hyperglycemia on arginine-induced insulin release were not significantly different from the ED 50 for glucose-induced insulin secretion (without arginine). When dose-response curves of plasma insulin increments were analyzed with the same equation, the ED 50 of second-phase glucose-induced plasma insulin increments was significantly higher than the ED 50 assessed from the plasma C-peptide increments (21.6 ± 2.8 v 14.3 ± 1.3 mmol/L, respectively, P < .05) We conclude (1) that the regulation by glucose of the two phases of insulin release involves (partly) different mechanisms in vivo, (2) that this difference in regulation occurs both in glucose- and in combined glucose-arginine-stimulated insulin release; (3) that combined glucose-arginine stimulation can be used as a tool for the assessment of B-cell glucose sensitivity; (4) that analysis using plasma insulin (instead of plasma C-peptide) increments can give a falsely high assessment for the parameter of the ED 50.