Skeletal muscle glucose uptake during treadmill exercise in neuronal nitric oxide synthase-μ knockout mice

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 (nNOS mu), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOS mu(+/+) and nNOS mu(-/-) 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 nNOS mu(+/+) and nNOS mu(-/-), 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 nNOS mu(-/-) mice, and exercise increased NOS activity only in nNOS mu(+/+) 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 mu(-/-) than in nNOS mu(+/+) mice (P < 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOS mu(-/-) mice. In conclusion, nNOS mu is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOS mu(-/-) mice may be due to compensatory increases in AMPK activation.