l-Arginine: An Ultradian-Regulated Substrate Coupled With Insulin Oscillations in Healthy Volunteers

Abstract

OBJECTIVE—Coupled oscillations of 50–110 min in insulin and glucose have been found previously in healthy men under continuous enteral nutrition. Because l-arginine induces insulin release as glucose does, we tested the hypothesis that l-arginine can also display such an ultradian rhythm. RESEARCH DESIGN AND METHODS—Seven healthy male subjects participated in one experimental night during which blood was sampled every 10 min from 2300 to 0700. Plasma glucose, C-peptide, and l-arginine levels were measured simultaneously. The insulin secretion rate (ISR) was calculated from plasma C-peptide levels by a deconvolution procedure. RESULTS—Plasma glucose followed the recognizable profiles, with oscillations closely linked to similar changes in the ISR. Pulse analysis of l-arginine profiles revealed significant oscillations linked to glucose and ISR oscillations, with the highest cross-correlation coefficients at time lag 0 ranging from 0.380 to 0.680 for glucose and l-arginine and from 0.444 to 0.726 for ISR and l-arginine (P < 0.01). The mean period of l-arginine oscillations was 77.2 ± 6.2 min, and their mean amplitude was 19.9 ± 1.7%, similar to that of glucose (17.0 ± 1.9%), when expressed as the percentage of mean overnight levels. CONCLUSIONS—This newly discovered ultradian rhythm of l-arginine and its coupling with glucose and ISR oscillations sheds new light on the regulation of l-arginine, the substrate of numerous metabolic pathways, including nitric oxide synthesis. These oscillations may be of significance in conditions of hyperinsulinemia or abnormal glucose tolerance.