Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects

• Published in: Diabetes (New York, N.Y.) Vol. 51; no. 8; pp. 2572 - 2580
• Main Authors: Kingwell, Bronwyn A., Formosa, Melissa, Muhlmann, Michael, Bradley, Scott J., McConell, Glenn K.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.08.2002
• Subjects: Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Blood Pressure - drug effects; Body Weight; Cholesterol - blood; Dextrose; Diabetes Mellitus, Type 2 - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Enzyme Inhibitors - pharmacology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Exercise; Exercise - physiology; Femoral Artery; Glucose; Glucose - metabolism; Glycated Hemoglobin A - analysis; Health aspects; Hemodynamics - drug effects; Humans; Insulin - blood; Lipoproteins - blood; Medical sciences; Middle Aged; Nitric oxide; Nitric Oxide Synthase - antagonists & inhibitors; omega-N-Methylarginine - pharmacology; Oxygen Consumption - physiology; Physiological aspects; Placebos; Reference Values; Regional Blood Flow; Triglycerides - blood; Type 2 diabetes; United States; Endocrinopathy; Physical exercise; Human; Enzyme; Enzyme inhibitor; Oxidoreductases; Glucose; Non insulin dependent diabetes; Uptake; Nitric-oxide synthase
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.51.8.2572

Nitric Oxide Synthase Inhibition Reduces Glucose Uptake During Exercise in Individuals With Type 2 Diabetes More Than in Control Subjects Bronwyn A. Kingwell 1 , Melissa Formosa 1 , Michael Muhlmann 1 , Scott J. Bradley 2 and Glenn K. McConell 3 1 Alfred and Baker Medical Unit, Baker Medical Research Institute, Prahran, Victoria, Australia 2 School of Physiotherapy, La Trobe University, Bundoora, Victoria, Australia 3 Department of Physiology, Monash University, Clayton, Victoria, Australia Abstract Nitric oxide (NO) synthase inhibition reduces leg glucose uptake during cycling without reducing leg blood flow (LBF) in young, healthy individuals. This study sought to determine the role of NO in glucose uptake during exercise in individuals with type 2 diabetes. Nine men with type 2 diabetes and nine control subjects matched for age, sex, peak pulmonary oxygen uptake ( V o 2 peak), and weight completed two 25-min bouts of cycling exercise at 60 ± 2% V o 2 peak, separated by 90 min. N G -monomethyl- l -arginine ( l -NMMA) (total dose 6 mg/kg) or placebo was administered into the femoral artery for the final 15 min of exercise in a counterbalanced, blinded, crossover design. LBF was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of LBF and femoral arteriovenous glucose difference. During exercise with placebo, glucose uptake was not different between control subjects and individuals with diabetes; however, LBF was lower and arterial plasma glucose and insulin levels were higher in individuals with diabetes. l -NMMA had no effect on LBF or arterial plasma glucose and insulin concentrations during exercise in both groups. l -NMMA significantly reduced leg glucose uptake in both groups, with a significantly greater reduction ( P = 0.04) in the diabetic group (75 ± 13%, 5 min after l -NMMA) compared with the control group (34 ± 14%, 5 min after l -NMMA). These data suggest a greater reliance on NO for glucose uptake during exercise in individuals with type 2 diabetes compared with control subjects. Footnotes Address correspondence and reprint requests to Dr. Bronwyn Kingwell, Alfred and Baker Medical Unit, Baker Medical Research Institute, P.O. Box 6492, St. Kilda Road Central, Melbourne 8008, Australia. E-mail: b.kingwell{at}alfred.org.au . Received for publication 20 June 2001 and accepted in revised form 10 April 2002. AMPK, AMP-activated protein kinase; a-v, arteriovenous; eNOS, endothelial nitric oxide synthase; LBF, leg blood flow; l -NMMA, N G -monomethyl- l -arginine; NOS, nitric oxide synthase; NO x , nitrate/nitrite; RER, respiratory exchange ratio; S o 2 , oxygen saturation; STPD, standard temperature and pressure, dry; V o 2 peak, peak pulmonary oxygen uptake. DIABETES