Publication: Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: Role of p38 MAPK
Issued Date
2009-11-15
Resource Type
ISSN
08915849
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2-s2.0-70350018326
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Mahidol University
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SCOPUS
Bibliographic Citation
Free Radical Biology and Medicine. Vol.47, No.10 (2009), 1486-1493
Suggested Citation
Tara L. Archuleta, Andrew M. Lemieux, Vitoon Saengsirisuwan, Mary K. Teachey, Katherine A. Lindborg, John S. Kim, Erik J. Henriksen Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: Role of p38 MAPK. Free Radical Biology and Medicine. Vol.47, No.10 (2009), 1486-1493. doi:10.1016/j.freeradbiomed.2009.08.014 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/27117
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Title
Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: Role of p38 MAPK
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Abstract
Oxidative stress is characterized as an imbalance between the cellular production of oxidants and the cellular antioxidant defenses and contributes to the development of numerous cardiovascular and metabolic disorders, including hypertension and insulin resistance. The effects of prolonged oxidant stress in vitro on the insulin-dependent glucose transport system in mammalian skeletal muscle are not well understood. This study examined the in vitro effects of low-level oxidant stress (60-90 μM, H2O2) for 4 h on insulin-stimulated (5 mU/ml) glucose transport activity (2-deoxyglucose uptake) and on protein expression of critical insulin signaling factors (insulin receptor (IR), IR substrates IRS-1 and IRS-2, phosphatidylinositol 3-kinase, Akt, and glycogen synthase kinase-3 (GSK-3)) in isolated soleus muscle of lean Zucker rats. This oxidant stress exposure caused significant (50%, p < 0.05) decreases in insulin-stimulated glucose transport activity that were associated with selective loss of IRS-1 (59%) and IRS-2 (33%) proteins, increased (64%) relative IRS-1 Ser307phosphorylation, and decreased phosphorylation of Akt Ser473(50%) and GSK-3β Ser9(43%). Moreover, enhanced (37%) phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was observed. Selective inhibition of p38 MAPK (10 μM A304000) prevented a significant portion (29%) of the oxidant stress-induced loss of IRS-1 (but not IRS-2) protein and allowed partial recovery of the impaired insulin-stimulated glucose transport activity. These results indicate that in vitro oxidative stress in mammalian skeletal muscle leads to substantial insulin resistance of distal insulin signaling and glucose transport activity, associated with a selective loss of IRS-1 protein, in part due to a p38 MAPK-dependent mechanism. © 2009 Elsevier Inc. All rights reserved.