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Normal increases in insulin-stimulated glucose uptake after ex vivo contraction in neuronal nitric oxide synthase mu (nNOSμ) knockout mice

  • Muscle physiology
  • Published:
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Abstract

Nitric oxide (NO) is involved in skeletal muscle glucose uptake during exercise and also in the increase in insulin sensitivity after exercise. Given that neuronal nitric oxide synthase (NOS) isoform mu (nNOSμ) is a major isoform of NOS in skeletal muscle, we examined if the increase in skeletal muscle insulin-stimulated glucose uptake 3.5 h following ex vivo contraction of extensor digitorum longus (EDL) is reduced in muscles from nNOSμ+/− and nNOSμ−/− mice compared with nNOSμ+/+ mice. 3.5 h post-contraction/basal, muscles were exposed to saline or insulin (120μU/ml) with or without the presence of the NOS inhibitor NG-monomethyl-L-arginine (L-NMMA) during the last 30 min and glucose uptake was determined by radioactive tracers. Skeletal muscle insulin-stimulated glucose uptake from nNOSμ+/+, nNOSμ+/−, and nNOSμ−/− mice increased approximately twofold 3.5 h following ex vivo contraction when compared to rest. L-NMMA significantly attenuated this increase in muscle insulin-stimulated glucose uptake by around 50%, irrespective of genotype. Low levels of NOS activity were detected in muscles from nNOSμ−/− mice. In conclusion, NO mediates increases in mouse skeletal muscle insulin response following ex vivo contraction independently of nNOSμ.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This study was funded by the National Health and Medical Research Council (NHMRC, Project grant number 1012181 to GKM) and the Diabetes Australia Research Trust (DART, Project grant number Y16G-ZHAM to XZ) in Australia.

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Authors and Affiliations

  1. Institute of Health and Sport (IHeS), Victoria University, Melbourne, Australia

    Xinmei Zhang, Xuzhu Lin & Glenn K. McConell

  2. School of Health and Biomedical Sciences, RMIT University, PO Box 71, Bundoora, Melbourne, VIC, 3083, Australia

    Xinmei Zhang

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  1. Xinmei Zhang
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Correspondence to Xinmei Zhang.

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Zhang, X., Lin, X. & McConell, G.K. Normal increases in insulin-stimulated glucose uptake after ex vivo contraction in neuronal nitric oxide synthase mu (nNOSμ) knockout mice. Pflugers Arch - Eur J Physiol 471, 961–969 (2019). https://doi.org/10.1007/s00424-019-02268-1

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