• 1 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
  • 2 Cellular and Molecular Metabolism, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia
Am J Physiol Endocrinol Metab, 2016 05 15;310(10):E838-45.
PMID: 27006199 DOI: 10.1152/ajpendo.00513.2015


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.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.