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Reactive oxygen species and nitric oxide, but not AMPK, mediate stretch‐induced glucose uptake by muscle.
Author(s) -
Smith Melissa A,
Goodyear Laurie J,
Reid Michael B
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.959.4
Subject(s) - catalase , ampk , reactive oxygen species , chemistry , superoxide dismutase , medicine , glucose uptake , nitric oxide , skeletal muscle , extensor digitorum longus muscle , endocrinology , ebselen , glucose transporter , protein kinase a , biochemistry , antioxidant , phosphorylation , glutathione peroxidase , insulin , biology , organic chemistry
Diabetes is characterized by a reduction in insulin‐stimulated signaling leading to impaired glucose uptake. An alternative pathway for glucose uptake can be stimulated by exercise and exogenous reactive oxygen species (ROS). We proposed a model wherein mechanical loading, i.e. stretch, stimulates production of ROS to activate AMP‐activated kinase (AMPK) to increase glucose uptake. Previously, we demonstrated stretch increases ROS, AMPK phosphorylation, and glucose transport in murine extensor digitorum longus (EDL) muscle. The current studies demonstrate that the ROS‐selective antioxidants ebselen (catalase mimetic) or combined superoxide dismutase (SOD)‐plus‐catalase suppress stretch‐induced oxidant activity (−20% vs. stretch p<0.05). In contrast, stretch‐induced glucose uptake persists in transgenic mice expressing an inactive form of the AMPKalpha2 catalytic subunit in skeletal muscle (+73% of basal p<0.05). MnTBAP, an SOD mimetic, N‐acteyl cysteine (NAC), a nonspecific antioxidant, and L‐NAME abolish stretch‐induced glucose uptake (2.26, 3.08, 2.88 vs. 4.57 μmol/ml/hr respectively p<0.05). Ebselen or combined SOD‐plus‐catalase decrease stretch‐induced glucose uptake (3.45, 3.68 vs. 4.57 μmol/ml/hr p<0.05, =0.07). These data indicate that stretch‐induced glucose uptake is mediated by a ROS‐dependent but AMPK‐independent mechanism. Supported by AHA 0615263B & DK 066232.