| Autor: |
Santos, Fernando Reyes, Diamond-Stanic, Maggie K., Prasannarong, Mujalin, Henriksen, Erik J. |
| Jazyk: |
angličtina |
| Rok vydání: |
2012 |
| Druh dokumentu: |
Text |
| Popis: |
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. |
| Databáze: |
Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
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