Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
Volume 60, Issue 1, Pages R1-R8Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-17-0151
Keywords
diabetes II; insulin action; insulin receptor; insulin signaling; liver
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [R01DK107641]
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Insulin resistance is the hallmark of type 2 diabetes; however, the mechanism underlying the development of insulin resistance is still not completely understood. Previous reports showed that posttranslational modifications of IRS play a critical role in insulin signaling, especially the phosphorylation of IRS by distinct kinases. While it is known that increasing Sirtuin1 deacetylase activity improves insulin sensitivity in the liver, the identity of its counterpart, an acetyl-transferase, remains unknown. Our recent study shows that elevated endotoxin (LPS) levels in the liver of obese mice lead to the induction of the acetyl-transferase P300 through the IRE1-XBP1s pathway. Subsequently, induced P300 impairs insulin signaling by acetylating IRS1 and IRS2 in the insulin signaling pathway. Therefore, the P300 acetyl-transferase activity appears to be a promising therapeutic target for the treatment of diabetes.
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