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    The Serine Kinase C-Jun N-Terminal Kinase (JNK) Contributes to Oxidant-Induced Insulin Resistance in Isolated Rat Skeletal Muscle

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    Author
    Santos, Fernando Reyes
    Diamond-Stanic, Maggie K.
    Prasannarong, Mujalin
    Henriksen, Erik J.
    Issue Date
    2012-05
    
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    Publisher
    The University of Arizona.
    Rights
    Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
    Abstract
    Insulin resistance of the mammalian skeletal muscle glucose transport system, one cause of which is oxidative stress, leads to the development of type 2 diabetes. While the direct contributions to insulin resistance of certain stress-activated serine kinases have been described previously, the specific contribution of c-Jun N-terminal kinase (JNK) is not fully understood. Therefore, we assessed the role of JNK in insulin resistance caused by in vitro exposure to the oxidant hydrogen peroxide (H₂O₂). Soleus muscles from lean Zucker rats were incubated in low levels (~30 μM) of H₂O₂ in the absence or presence of insulin for up to 6 hr. Decreases in insulin-stimulated glucose transport activity (ISGTA) were observed at all time points and were associated with similar diminutions in insulin stimulation of Akt Ser⁴⁶⁷ phosphorylation. Phosphorylation (Thr¹⁸³/Tyr¹⁸⁵) of JNK isoforms (JNK1 and JNK2/3) was increased by H₂O₂ in the absence and presence of insulin at all time points. To determine the specific contribution of JNK to oxidant-induced insulin resistance, the JNK inhibitor SP600125 was used. ISGTA in the presence of H₂O₂ was improved when the inhibitor was added during the 6-hr incubation. These results indicate that JNK contributes to oxidative stress-induced insulin resistance in mammalian skeletal muscle.
    Type
    text
    Electronic Thesis
    Degree Name
    B.S.H.S.
    Degree Level
    bachelors
    Degree Program
    Honors College
    Physiology
    Degree Grantor
    University of Arizona
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    Honors Theses
    Honors Theses

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