title: Skeletal muscle glucose uptake during treadmill exercise in neuronal nitric oxide synthase-μ knockout mice.
abstract: Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ(+/+) and nNOSμ(-/-) mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 ± 0.6 vs. 15.9 ± 0.9 min for nNOSμ(+/+) and nNOSμ(-/-), respectively, P > 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSμ(-/-) mice, and exercise increased NOS activity only in nNOSμ(+/+) mice (4.4 ± 0.3 to 5.2 ± 0.4 pmol·mg(-1)·min(-1), P < 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSμ(-/-) than in nNOSμ(+/+) mice (P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSμ(-/-) mice. In conclusion, nNOSμ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSμ(-/-) mice may be due to compensatory increases in AMPK activation.
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia; Clinical Exercise Science Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia; Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; and yhhong0530@um.edu.my.
authors.forename: Yet Hoi
authors.initials: YH
authors.lastname: Hong
authors.affiliation: Cellular and Molecular Metabolism, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Yang
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia; Clinical Exercise Science Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia;
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Betik
authors.affiliation: Cellular and Molecular Metabolism, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Lee-Young
authors.affiliation: College of Health and Biomedicine, Victoria University, Melbourne, Victoria, Australia; Clinical Exercise Science Program, Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Victoria, Australia;
authors.forename: Glenn K
authors.initials: GK
authors.lastname: McConell
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000235:genetics*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal
chemical_list: D001786:Blood Glucose; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: AMPK; glucose transport; nitric oxide