Dose-Response Characteristics for Arginine-Stimulated Insulin Secretion in Man and Influence of Hyperglycemia *

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Abstract
To test the hypothesis that glucose only affects the responsiveness (maximum velocity) of the β-cell to arginine without changing the sensitivity (ED50) of the β-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 < 0.002). Hyperglycemia significantly increased arginine-induced insulin secretion at all arginine infusion rates (P < 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.

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