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.


METHODS
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.


CONCLUSIONS
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.
Stingl
Harald
H
Division of Endocrinology and Metabolism, Department of Internal Medicine III, University of Vienna Medical School, Vienna, Austria.
Raffesberg
Wolfgang
W
Nowotny
Peter
P
Waldhäusl
Werner
W
Roden
Michael
M
D000328:Adult; D001120:Arginine / Q000008:administration & dosage*; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000008:administration & dosage / Q000097:blood; D005990:Glycerol / Q000008:administration & dosage; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000097:blood; D007700:Kinetics; D020738:Leptin / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013004:Somatostatin / Q000008:administration & dosage
D002096:C-Peptide; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D020738:Leptin; D013004:Somatostatin; D006493:Heparin; D005934:Glucagon; D001120:Arginine; D005990:Glycerol