title: Attenuation of oxidant-induced muscle insulin resistance and p38 MAPK by exercise training.
abstract: We have recently shown that direct exposure to an oxidant stress induces resistance to insulin in glucose transport activity in intact rat skeletal muscle. In this study, we evaluated the effectiveness of prior exercise training in attenuating oxidative stress-induced insulin resistance. Male Sprague-Dawley rats either remained sedentary or underwent a treadmill-running regimen for 6 weeks. Isolated soleus muscles were incubated in the absence or presence of hydrogen peroxide (H(2)O(2)) (50-70 microM) with or without insulin for 2 h. In the sedentary animals, H(2)O(2) significantly inhibited insulin action on glucose transport activity and phosphorylation of Akt (Ser(473)), by 28 and 24%, respectively, and substantially activated the phosphorylation levels of p38 MAPK (Thr(180)/Tyr(182)) by 43% and SAPK/JNK (Thr(183)/Tyr(185)) by 111%. Interestingly, the inhibitory effects of H(2)O(2) on insulin-stimulated glucose transport and Akt (Ser(473)) phosphorylation were attenuated by 43 and 75% in exercise-trained muscles. Additionally, the phosphorylation level of p38 MAPK (Thr(180)/Tyr(182)) triggered by oxidative stress was reduced by 59% in the exercise-trained muscle. We have demonstrated for the first time in mammalian skeletal muscle that endurance exercise training can partially protect against glucose transport resistance to insulin induced by oxidative stress, and this benefit of exercise training is at least in part mediated through the insulin signaling pathway and stress-activated signaling elements.
authors.affiliation: Exercise Physiology Laboratory, Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok 10400, Thailand.
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Vichaiwong
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Henriksen
authors.forename: Chaivat
authors.initials: C
authors.lastname: Toskulkao
authors.forename: Mujalin
authors.initials: M
authors.lastname: Prasannarong
authors.forename: Tepmanas
authors.initials: T
authors.lastname: Bupha-Intr
authors.forename: Vitoon
authors.initials: V
authors.lastname: Saengsirisuwan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009929:Organ Size; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016877:Oxidants; D000255:Adenosine Triphosphate; D002950:Citrate (si)-Synthase; D048051:p38 Mitogen-Activated Protein Kinases