Dose-response characteristics for arginine-stimulated insulin secretion in man and influence of hyperglycemia.
To test the hypothesis that glucose only affects the responsiveness (maximum velocity) of the beta-cell to arginine without changing the sensitivity (ED50) of the beta-cell to arginine, we investigated the influence of hyperglycemia on the responsiveness and sensitivity of arginine-induced insulin secretion in eight healthy male volunteers. Plasma C-peptide and insulin levels achieved during infusions of five doses of arginine (30 min) with and without a 60-min hyperglycemic clamp (17 mmol/L) were analyzed using a modified Michaelis-Menten equation. At euglycemia, the ED50 (half-maximally stimulating serum arginine concentration) was significantly less for first phase than for second phase plasma C-peptide secretion (0.7 +/- 0.1 vs. 2.7 +/- 0.4 mmol/L; P less than 0.002). Hyperglycemia significantly increased arginine-induced insulin secretion at all arginine infusion rates (P less than 0.01) without significantly altering the ED50 for either phase. We conclude 1) that the regulation of arginine-induced insulin secretion differs between both phases of insulin secretion, and 2) that a 1-h infusion with glucose significantly potentiates arginine-induced insulin secretion without influencing the difference in regulation of both phases of arginine-induced insulin secretion, supporting the validity of the use of arginine as a secretagogue in studies involving hyperglycemia.
van Haeften
T W
TW
Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
Voetberg
G A
GA
Gerich
J E
JE
van der Veen
E A
EA
D000328:Adult; D001120:Arginine / Q000008:administration & dosage* / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D001800:Blood Specimen Collection; D002096:C-Peptide / Q000097:blood; D004305:Dose-Response Relationship, Drug; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood*; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D008433:Mathematics
D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D001120:Arginine