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JNK signaling pathways is required for mitochondrial dysfunction-induced iinsulin resistance in WRL-68 human liver cell

Abu Bakar, Mohamad Hafizi and Sarmidi, Mohamad Roji and Yaakob, Harisun and Cheng, Kian Kai and Zaman Huri, Hasniza (2015) JNK signaling pathways is required for mitochondrial dysfunction-induced iinsulin resistance in WRL-68 human liver cell. Diabetes Technology & Therapeutics, 17 . A154-A155. ISSN 1520-9156

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Mitochondrial dysfunction and metabolic inflammation have emerged as the key events underpinning the development of obesity-related insulin resistance and type 2 diabetes. Accumulating evidence indicates that c-Jun NH(2)-terminal kinase (JNK) signaling pathways are among the regulatory pathways responsible for oxidative stress linked inflammation in the development of hepatic insulin resistance. So far, little is known about the upstream roles of JNK signaling pathways in maintaining adequate energy balance relative to mitochondrial functions in hepatocytes. Therefore, the aim of this study was to investigate the therapeutic roles of JNK signaling pathways inhibition upon mitochondrial dysfunction-induced insulin resistance in WRL-68 human liver cells. We found that JNK inhibitor (SP600125) exhibits ameliorative properties in cells treated with rotenone, mitochondrial complex I inhibitor via enhancement of insulin stimulated-glucose uptake activity. The increased phosphorylation of insulin signaling activities via IRS1, Akt/PKB and AS160 was observed. The augmented level of oxidative DNA damage, protein carbonylation and lipid peroxidation in hepatocytes with mitochondrial dysfunctions was prevented by JNK inhibitor. In addition, rotenone caused massive production of pro-inflammatory mediators IL-6, TNF-a and IL-1ß by altering inflammatory signaling pathways whereas JNK inhibitor counteracted all these parameters in insulin-resistant cells. In summary, we showed that JNK inhibitor could prevent mitochondrial dysfunction and insulin resistance via inhibition of JNK signaling pathways. Together, these discoveries for the first time identify JNK signaling pathways as one of the therapeutic regulators of mitochondrial dysfunction in hepatic tissue insulin resistance and inflammation.

Item Type:Article
Uncontrolled Keywords:human liver cell, mitochondrial dysfunction
Subjects:R Medicine > R Medicine (General)
Divisions:Biosciences and Medical Engineering
ID Code:58458
Deposited By: Haliza Zainal
Deposited On:04 Dec 2016 04:07
Last Modified:18 Sep 2017 01:31

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