title: 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.affiliation: Department of Geratology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Yao
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Meihong
authors.initials: M
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Su
authors.initials: S
authors.lastname: Peng
authors.affiliation: Department of Geratology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Kaixuan
authors.initials: K
authors.lastname: Li
authors.affiliation: School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Muchen
authors.initials: M
authors.lastname: Xu
authors.affiliation: School of Medicine, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China.
authors.forename: Ningmei
authors.initials: N
authors.lastname: Shen
authors.affiliation: Department of Geratology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, People's Republic of China. Electronic address: chinaluolan@hotmail.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Luo
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, Jiangsu 226001, People's Republic of China. Electronic address: suncheng1975@ntu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D055316:Cystatin C / Q000037:antagonists & inhibitors / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007328:Insulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D010654:Phenylbutyrates / Q000494:pharmacology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C525030:CST3 protein, human; C525031:Cst3 protein, mouse; D055316:Cystatin C; D007328:Insulin; D010654:Phenylbutyrates; D011994:Recombinant Proteins; C075773:4-phenylbutyric acid
keywords: Cystatin C; ER stress; Insulin signal transduction; Obesity; Type 2 diabetes; Unfolded protein response