Glucose uptake during contraction in isolated skeletal muscles from neuronal nitric oxide synthase μ knockout mice.

Abstract

Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.

• Authors: Yet Hoi Hong, Tony Frugier, Xinmei Zhang, Robyn M Murphy, Gordon S Lynch, Andrew C Betik, Stephen Rattigan, Glenn K McConell
• Journal: Journal of applied physiology (Bethesda, Md. : 1985) (J Appl Physiol (1985)) Vol. 118 Issue 9 Pg. 1113-21 (May 01 2015) ISSN: 1522-1601 [Electronic] United States
• PMID: 25749441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Enzyme Inhibitors
• omega-N-Methylarginine
• Nitric Oxide
• Arginine
• Nitric Oxide Synthase Type I
• Nos1 protein, mouse
• AMP-Activated Protein Kinases
• Glucose

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Arginine (metabolism)
• Biological Transport (drug effects, physiology)
• Enzyme Inhibitors (pharmacology)
• Female
• Glucose (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Muscle Contraction (drug effects, physiology)
• Muscle, Skeletal (drug effects, metabolism, physiology)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type I (metabolism)
• Physical Conditioning, Animal (physiology)
• omega-N-Methylarginine (pharmacology)