Premium
Stretch‐stimulated glucose uptake in skeletal muscle is mediated by reactive oxygen species and p38 MAP‐kinase
Author(s) -
Chambers Melissa A.,
Moylan Jennifer S.,
Smith Jeffrey D.,
Goodyear Laurie J.,
Reid Michael B.
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2008.165639
Subject(s) - skeletal muscle , reactive oxygen species , chemistry , p38 mitogen activated protein kinases , microbiology and biotechnology , mitogen activated protein kinase , glucose uptake , biophysics , biochemistry , kinase , protein kinase a , biology , endocrinology , insulin
Alternatives to the canonical insulin‐stimulated pathway for glucose uptake are exercise‐ and exogenous reactive oxygen species (ROS)‐stimulated glucose uptake. We proposed a model wherein mechanical loading, i.e. stretch, stimulates production of ROS to activate AMP‐activated kinase (AMPK) to increase glucose uptake. Immunoblotting was used to measure protein phosphorylation; the fluorochrome probe 2′7′‐dichlorofluorescin diacetate was used to measure cytosolic oxidant activity and 2‐deoxy‐ d [1,2‐ 3 H]glucose was used to measure glucose uptake. The current studies demonstrate that stretch increases ROS, AMPKα phosphorylation and glucose transport in murine extensor digitorum longus (EDL) muscle (+121%, +164% and +184%, respectively; P < 0.05). We also demonstrate that stretch‐induced glucose uptake persists in transgenic mice expressing an inactive form of the AMPKα2 catalytic subunit in skeletal muscle (+173%; P < 0.05). MnTBAP, a superoxide dismutase (SOD) mimetic, N ‐acteyl cysteine (NAC), a non‐specific antioxidant, ebselen, a glutathione mimetic, or combined SOD plus catalase (ROS‐selective scavengers) all decrease stretch‐stimulated glucose uptake ( P < 0.05) without changing basal uptake ( P > 0.16). We also demonstrate that stretch‐stimulated glucose uptake persists in the presence of the phosphatidylinositol 3‐kinase (PI3‐K) inhibitors wortmannin and LY294001 ( P < 0.05) but is diminished by the p38‐MAPK inhibitors SB203580 and A304000 ( P > 0.99). These data indicate that stretch‐stimulated glucose uptake in skeletal muscle is mediated by a ROS‐ and p38 MAPK‐dependent mechanism that appears to be AMPKα2‐ and PI3‐K‐independent.