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Nitric oxide is required for the insulin sensitizing effects of contraction in mouse skeletal muscle

Zhang, X, Hiam, D, Hong, YH, Zulli, A, Hayes, A, Rattigan, S ORCID: 0000-0001-6172-3040 and McConell, GK 2017 , 'Nitric oxide is required for the insulin sensitizing effects of contraction in mouse skeletal muscle' , Journal of Physiology, vol. 595, no. 24 , pp. 7427-7439 , doi: 10.1113/JP275133.

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Abstract

The factors regulating the increase in skeletal muscle insulin sensitivity after exercise are unclear. We examined whether nitric oxide (NO) is required for the increase in insulin sensitivity after ex vivo contractions. Isolated C57BL/6J mouse EDL muscles were contracted for 10 min or remained at rest (basal) with or without the NO synthase (NOS) inhibition (NG -monomethyl-L-arginine; L-NMMA; 100 μm). Then, 3.5 h post contraction/basal, muscles were exposed to saline or insulin (120 μU ml-1 ) with or without L-NMMA during the last 30 min. L-NMMA had no effect on basal skeletal muscle glucose uptake. The increase in muscle glucose uptake with insulin (57%) was significantly (P < 0.05) greater after prior contraction (140% increase). NOS inhibition during the contractions had no effect on this insulin-sensitizing effect of contraction, whereas NOS inhibition during insulin prevented the increase in skeletal muscle insulin sensitivity post-contraction. Soluble guanylate cyclase inhibition, protein kinase G (PKG) inhibition or cyclic nucleotide phosphodiesterase inhibition each had no effect on the insulin-sensitizing effect of prior contraction. In conclusion, NO is required for increases in insulin sensitivity several hours after contraction of mouse skeletal muscle via a cGMP/PKG independent pathway.

Item Type: Article
Authors/Creators:Zhang, X and Hiam, D and Hong, YH and Zulli, A and Hayes, A and Rattigan, S and McConell, GK
Keywords: L-NMMA, insulin sensitivity, muscle contraction
Journal or Publication Title: Journal of Physiology
Publisher: Cambridge Univ Press
ISSN: 0022-3751
DOI / ID Number: 10.1113/JP275133
Copyright Information:

© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society

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