Contribution of the serine kinase c-Jun N-terminal kinase (JNK) to oxidant-induced insulin resistance in isolated rat skeletal muscle.
The specific and direct contribution of the stress-activated serine kinase c-Jun N-terminal kinase (JNK) in the development of oxidative stress-induced insulin resistance of the glucose transport system in mammalian skeletal muscle is not fully understood. We assessed the specific role of JNK in the development of insulin resistance caused by in vitro exposure of rat soleus muscle to low levels (30-40 µM) of the oxidant hydrogen peroxide (H(2)O(2)) for up to 6 h. Oxidant exposure caused significant (p < 0.05) decreases in insulin-stimulated glucose transport activity (up to 42%) and Akt Ser(473) phosphorylation (up to 67%), and increased (up to 74%) phosphorylation (Thr(183)/Tyr(185)) of JNK1 and JNK2/3 isoforms. Importantly, insulin-stimulated glucose transport activity in the presence of H(2)O(2) was moderately improved with the selective JNK inhibitor SP600125. These results indicate that activation of the serine kinase JNK contributes, at least in part, to oxidative stress-induced insulin resistance in isolated mammalian skeletal muscle.
Muscle Metabolism Laboratory, Department of Physiology, University of Arizona, College of Medicine, Tucson, AZ 85724, USA.
Fernando R
FR
Santos
Maggie K
MK
Diamond-Stanic
Mujalin
M
Prasannarong
Erik J
EJ
Henriksen
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007333:Insulin Resistance; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects
D000873:Anthracenes; D007527:Isoenzymes; D016877:Oxidants; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D006861:Hydrogen Peroxide; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose