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• W1489245211 startingPage "3363" @default.
• W1489245211 abstract "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." @default.
• W1489245211 created "2016-06-24" @default.
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• W1489245211 date "2009-06-30" @default.
• W1489245211 modified "2023-10-16" @default.
• W1489245211 title "Stretch-stimulated glucose uptake in skeletal muscle is mediated by reactive oxygen species and p38 MAP-kinase" @default.
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• W1489245211 doi "https://doi.org/10.1113/jphysiol.2008.165639" @default.
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