L-arginine-nitric oxide kinetics in normal and type 2 diabetic subjects: a stable-labelled 15N arginine approach.
Defective endothelium is a key event in the development of atherosclerosis in diabetes: alteration of the L-arginine-nitric oxide (NO) pathway has been suggested. We propose a modeling approach of the L-arginine-NO pathway in vivo in both control and type 2 diabetic subjects based on the intravenous bolus injection of L-[(15)N]arginine and subsequent noncompartmental and compartmental model analysis of L-[(15)N] arginine in plasma and [(15)N]nitrate in the urine. No differences in arginine kinetics were observed between normal subjects and diabetic patients. [(15)N]nitrates were detectable up to 48 h from the L-(15)[N]arginine administration; no differences were found in the tracer-to-tracee ratio in each urine collection. However, the NO synthesis in plasma from arginine was lower (P = 0.05 for the noncompartmental and 0.1208 for the compartmental analysis, by Mann-Whitney test) in diabetic patients than in control subjects when expressed both in absolute terms (50% decrease) and as percentage of NO turnover (30% decrease). This new modeling approach of L-arginine-NO pathway provides a detailed picture of arginine kinetics and nitrate metabolism. From our data, it appears that noncomplicated type 2 diabetic patients have a decreased conversion of arginine to NO.
Avogaro
Angelo
A
Department of Metabolic Disease, University of Padua, Via Giustiniani 2, 35128 Padua, Italy. angelo.avogaro@unipd.it
Toffolo
Gianna
G
Kiwanuka
Edward
E
de Kreutzenberg
Saula Vigili
SV
Tessari
Paolo
P
Cobelli
Claudio
C
D001120:Arginine / Q000097:blood / Q000493:pharmacokinetics*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008297:Male; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism*; D009587:Nitrogen Isotopes
D009566:Nitrates; D009587:Nitrogen Isotopes; D009569:Nitric Oxide; D001120:Arginine