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 nNOS µ-/-than in nNOS µ+/+ mice (P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOS µ-/-mice. In conclusion, nNOSµ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOS µ-/-mice may be due to compensatory increases in AMPK activation.