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 mu (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 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/min, P < 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5 to 7-fold) and surprisingly, more so in nNOSμ-/- than 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.
- glucose uptake
- nitric oxide
- Copyright © 2016, American Journal of Physiology - Endocrinology and Metabolism