Role of oxidative stress in impaired insulin signaling associated with exercise-induced muscle damage.
Skeletal muscle is a major tissue that utilizes blood glucose. A single bout of exercise improves glucose uptake in skeletal muscle through insulin-dependent and insulin-independent signal transduction mechanisms. However, glucose utilization is decreased in muscle damage induced by acute, unaccustomed, or eccentric exercise. The decrease in glucose utilization is caused by decreased insulin-stimulated glucose uptake in damaged muscles with inhibition of the membrane translocation of glucose transporter 4 through phosphatidyl 3-kinase/Akt signaling. In addition to inflammatory cytokines, reactive oxygen species including 4-hydroxy-2-nonenal and peroxynitrate can induce degradation or inactivation of signaling proteins through posttranslational modification, thereby resulting in a disturbance in insulin signal transduction. In contrast, treatment with factors that attenuate oxidative stress in damaged muscle suppresses the impairment of insulin sensitivity. Muscle-damaging exercise may thus lead to decreased endurance capacity and muscle fatigue in exercise, and it may decrease the efficiency of exercise therapy for metabolic improvement.
Laboratory of Health Science, Graduate School of Life and Environmental Sciences, Kyoto Prefectural University, Kyoto 606-8522, Japan. Electronic address: waoi@kpu.ac.jp.
Wataru
W
Aoi
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Yuji
Y
Naito
Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.
Toshikazu
T
Yoshikawa
D000447:Aldehydes; D001693:Biological Transport, Active; D015444:Exercise; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000037:antagonists & inhibitors; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D018763:Muscle Fatigue / Q000502:physiology*; D018482:Muscle, Skeletal / Q000293:injuries* / Q000473:pathology; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010807:Physical Endurance / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
D000447:Aldehydes; D051275:Glucose Transporter Type 4; D007328:Insulin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; C027576:4-hydroxy-2-nonenal
4-HNE; 4-Hydroxynonenal; 4-hydroxy-2-nonenal; AMP-activated kinase; AMPK; CK; Ca(2+)/calmodulin-dependent protein kinase; CaMK; Delayed-onset muscle damage; GLUT4; IKK; IL; IRS; Insulin signal transduction; IκB kinase; MAPK; Muscle-damaging exercise; NF-κB; PGC-1α; PI3-K; ROS; SOD; TNF-α; creatine kinase; glucose transporter 4; insulin receptor substrate; interleukin; mitogen-activated protein kinase; nuclear factor-κB; peroxisome proliferator-activated receptor γ coactivator-1α; phosphatidylinositol 3-kinase; reactive oxygen species; superoxide dismutase; tumor necrosis factor-α