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 approximately 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 approximately 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 ( approximately 35 pM) -glucagon ( approximately 90 ng/mL) clamps were performed. In both protocols, plasma leptin continuously declined by approximately 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.