Cystatin C attenuates insulin signaling transduction by promoting endoplasmic reticulum stress in hepatocytes.

Abstract	It has been reported that cystatin c (Cys C) closely correlates with metabolic disorders such as obesity and diabetes. However, it is still unknown whether Cys C plays a role for these disorders. Our results showed that the insulin signal transduction was largely impaired by Cys C in hepatocytes. In myotubes, however, the insulin signal transduction was not affected. Following experiments revealed that Cys C could induce endoplasmic reticulum stress (ER stress) in hepatocytes, whereas Cys C had no such an effect in myotubes. The alleviation of ER stress by 4-Phenyl butyric acid (4-PBA) restored the impaired insulin signal transduction in Cys C-treated hepatocytes. These results provided direct evidence that, by inducing ER stress, Cys C impairs insulin signal transduction in hepatocytes.
Authors	Xiaolin Ji, Lili Yao, Meihong Wang, Xiaoyu Liu, Su Peng, Kaixuan Li, Muchen Xu, Ningmei Shen, Lan Luo, Cheng Sun
Journal	FEBS letters (FEBS Lett) Vol. 589 Issue 24 Pt B Pg. 3938-44 (Dec 21 2015) ISSN: 1873-3468 [Electronic] England
PMID	26592151 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright	Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Chemical References	Antineoplastic Agents CST3 protein, human Cst3 protein, mouse Cystatin C Insulin Phenylbutyrates Recombinant Proteins 4-phenylbutyric acid
Topics	Animals Antineoplastic Agents (pharmacology) Cell Line Cells, Cultured Cystatin C (antagonists & inhibitors, blood, genetics, metabolism) Diabetes Mellitus, Type 2 (blood, metabolism) Down-Regulation (drug effects) Endoplasmic Reticulum Stress (drug effects) Gene Expression Regulation (drug effects) Hepatocytes (cytology, drug effects, metabolism, pathology) Humans Insulin (chemistry, genetics, metabolism) Male Mice, Inbred C57BL Mice, Mutant Strains Muscle Fibers, Skeletal (drug effects, metabolism) Organ Specificity Phenylbutyrates (pharmacology) Recombinant Proteins (chemistry, metabolism) Signal Transduction (drug effects) Up-Regulation (drug effects)

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