Authors: Bjorn T Tam Xiao M Pei Benjamin Y Yung Shea P Yip Lawrence W Chan Cesar S Wong Parco M Siu
Publish Date: 2015/07/31
Volume: 467, Issue: 12, Pages: 2555-2569
Abstract
Impairment of insulin signaling in skeletal muscle detrimentally affects insulinstimulated disposal of glucose Restoration of insulin signaling in skeletal muscle is important as muscle is one of the major sites for disposal of blood glucose Recently unacylated ghrelin UnAG has received attention in diabetic research due to its favorable actions on improving glucose tolerance glycemic control and insulin sensitivity The investigation of UnAG has entered phase Ib clinical trial in type 2 diabetes and phase II clinical trial in hyperphagia in PraderWilli syndrome Nonetheless the precise mechanisms responsible for the antidiabetic actions of UnAG remain incompletely understood In this study we examined the effects of UnAG on restoring the impaired insulin signaling in skeletal muscle of db/db diabetic mice Our results demonstrated that UnAG effectively restored the impaired insulin signaling in diabetic muscle UnAG decreased insulin receptor substrate IRS phosphorylation increased protein kinase B Akt phosphorylation and hence suppressed mTOR signaling Consequently UnAG enhanced Glut4 localization and increased PDH activity in the diabetic skeletal muscle Intriguingly our data indicated that UnAG normalized the suppressed autophagic signaling in diabetic muscle In conclusion our findings illustrated that UnAG restored the impaired insulin and autophagic signaling in skeletal muscle of diabetic mice which are valuable to understand the underlying mechanisms of the antidiabetic action of UnAG at peripheral skeletal muscle level
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