Passive stretch regulates skeletal muscle glucose uptake independent of nitric oxide synthase

Jarrod P. Kerris, Andrew C. Betik, Jinhua Li, Glenn K. McConell

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4 Citations (Scopus)


Skeletal muscle contraction increases glucose uptake via an insulin-independent mechanism. Signaling pathways arising from mechanical strain are activated during muscle contractions, and mechanical strain in the form of passive stretching stimulates glucose uptake. However, the exact mechanisms regulating stretch-stimulated glucose uptake are not known. Since nitric oxide synthase (NOS) has been implicated in the regulation of glucose uptake during ex vivo and in situ muscle contractions and during exercise, and NO is increased with stretch, we examined whether the increase in muscle glucose uptake during stretching involves NOS. We passively stretched isolated extensor digitorum longus muscles (15 min at ~100 –130 mN) from control mice and mice lacking either neuronal NOS (nNOS) or endothelial NOS (eNOS) isoforms, as well as used pharmacological inhibitors of NOS. Stretch significantly increased muscle glucose uptake appoxi-mately twofold (P 0.05), and this was unaffected by the presence of the NOS inhibitors N G -monomethyl-L-arginine (100 M) or N G -nitro-L-arginine methyl ester (100 M). Similarly, stretch-stimulated glucose uptake was not attenuated by deletion of either eNOS or nNOS isoforms. Furthermore, stretching failed to increase skeletal muscle NOS enzymatic activity above resting levels. These data clearly demonstrate that stretch-stimulated skeletal muscle glucose uptake is not dependent on NOS.

Original languageEnglish
Pages (from-to)239-245
Number of pages7
JournalJournal of Applied Physiology
Issue number1
Publication statusPublished - Jan 2019


  • Glucose uptake
  • Nitric oxide synthase
  • Skeletal muscle
  • Stretch

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