l-Arginine-Nitric Oxide Kinetics in Normal and Type 2 Diabetic Subjects
A Stable-Labelled 15N Arginine Approach
- Angelo Avogaro1,
- Gianna Toffolo2,
- Edward Kiwanuka1,
- Saula Vigili de Kreutzenberg1,
- Paolo Tessari1 and
- Claudio Cobelli2
- 1Department of Metabolic Disease, University of Padova, Padova, Italy
- 2Department of Information Engineering, University of Padova, Padova, Italy
Abstract
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-[15N]arginine and subsequent noncompartmental and compartmental model analysis of l-[15N] arginine in plasma and [15N]nitrate in the urine. No differences in arginine kinetics were observed between normal subjects and diabetic patients. [15N]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.
Footnotes
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Address correspondence and reprint requests to Angelo Avogaro, MD, Cattedra di Malattie del Metabolismo, Via Giustiniani 2, 35128 Padova, Italy. E-mail: angelo.avogaro{at}unipd.it.
Received for publication 18 August 2002 and accepted in revised form 2 December 2002
Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.
FSR, fractional synthetic rate; IRMS, isotope ratio mass-spectrometry.
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