A decrease in glucose production is associated with an increase in plasma citrulline response to oral arginine in normal volunteers

Abstract

Acute arginine administration (30 g) increases insulin secretion and reduces glucose production (GP). A slower administration of l-arginine may have direct effect on the liver without increasing C-peptide or insulin secretion. We tested the direct effect of oral l-arginine on fasting GP in 15 normal-weight volunteers and compared these to a group of l-alanine-treated controls (placebo). Volunteers were admitted to the General Clinical Research Center for a 3-day stay. Three grams of freebase arginine or alanine was ingested hourly between 4 am and 2 pm. Neither arginine nor alanine had an effect on C-peptide or insulin concentration. Oral arginine, but not alanine, increased plasma arginine, citrulline, and ornithine concentrations. Arginine-treated volunteers had a greater fall in GP as compared to the alanine-treated group (16.2% ± 1.9% v 9.7% ± 3.6%, respectively; P < .05). Five volunteers treated with arginine had less than a 30% increase in citrulline concentration (26 ± 2 to 32 ± 2 μmol/L, mean ± SEM) and 10 volunteers had equal to or greater than a 30% increase in plasma citrulline concentration (29 ± 2 to 49 ± 4 μmol/L, P <.05). Since citrulline is generated in the conversion of arginine to nitric oxide (NO), the failure of oral arginine to increase citrulline concentration suggests that NO generation may be varied in different individuals. The increased plasma citrulline group reduced GP by 18.2% ± 1.9% over the final 4 hours of arginine administration (2.00 ± 0.08 to 1.64 ± 0.07 mg/kg/min; P < .01). In contrast, GP only decreased by 12.4% ± 3.9% (1.97 ± 0.13 to 1.73 ± 0.13 mg/kg/min; not significant [NS]) in those who had little to no increase in plasma citrulline concentration. The 12% decrease in GP in the hyporesponders was similar to the 10% decrease seen in the alanine-treated normal volunteers (9.7% ± 3.6%). Individuals may have a variable NO response from an oral arginine administration. GP is suppressed in those who have a greater increase in plasma citrulline concentration.