Dose-response characteristics for glucose-stimulated insulin release in man and assessment of influence of glucose on arginine-stimulated insulin release.
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 ED50 (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 ED50 for the second phase (60 minutes; 8.4 +/- 0.8 v 14.3 +/- 1.3 mmol/L, respectively, P less than .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 less than .05). The ED50 of the influence of glucose on first-phase arginine-induced insulin release was significantly lower than the ED50 for the second phase (9.0 +/- 1.1 v 12.7 +/- 1.0 mmol/L, respectively, P less than .02). For each insulin secretion phase separately, the ED50 for the influence of hyperglycemia on arginine-induced insulin release were not significantly different from the ED50 for glucose-induced insulin secretion (without arginine). When dose-response curves of plasma insulin increments were analyzed with the same equation, the ED50 of second-phase glucose-induced plasma insulin increments was significantly higher than the ED50 assessed from the plasma C-peptide increments (21.6 +/- 2.8 v 14.3 +/- 1.3 mmol/L, respectively, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
van Haeften
T W
TW
Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
Boonstra
E
E
Veneman
T F
TF
Gerich
J E
JE
van der Veen
E A
EA
D000328:Adult; D001120:Arginine / Q000494:pharmacology*; D002096:C-Peptide / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007003:Hypoglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male
D002096:C-Peptide; D007328:Insulin; D001120:Arginine; D005947:Glucose