Reduction of Plasma Leptin Concentrations by Arginine but Not Lipid Infusion in Humans

Objective: We examined short-term effects of arginine infusion on plasma leptin in diabetic and healthy subjects. Research Methods and Procedures: Arginine stimulation tests were performed in C-peptide negative type 1 [DM1; hemoglobin A_1c; 7.3 ± 0.3%], hyperinsulinemic type 2 diabetic (DM2; 7.6 ± 0.7%), and nondiabetic subjects (CON; 5.4 ± 0.1%). Results: Fasting plasma leptin correlated linearly with body mass index among all groups (r = 0.61, p = 0.001). During arginine infusion, peak plasma insulin was lower in DM1 than in DM2 (p < 0.05) and CON (p < 0.01). Plasma leptin decreased within 30 minutes by ∼11% in DM1 (p < 0.001), DM2 (p < 0.01), and CON (p < 0.005), slowly returning to baseline thereafter. Plasma free fatty acids (FFAs) were higher in DM1 (0.6 ± 0.1 mM) and DM2 (0.6 ± 0.1 mM) than in CON (0.4 ± 0.1 mM, p < 0.05) and transiently declined by ∼50% (p < 0.05) at 45 minutes in all groups before rebounding toward baseline. To examine the direct effects of FFAs on plasma leptin, we infused healthy subjects with lipid/heparin and glycerol during fasting, and somatostatin-insulin (∼35 pM) -glucagon (∼90 ng/mL) clamps were performed. In both protocols, plasma leptin continuously declined by ∼25% (p < 0.05) during 540 minutes without any difference between the high and low FFA conditions. Discussion: Arginine infusion transiently decreased plasma leptin concentrations both in insulin-deficient and hyperinsulinemic diabetic patients, indicating a direct inhibitory effect of the amino acid but not of insulin or FFAs.