Diabetes-Induced Hepatic Pathogenic Damage, Inflammation, Oxidative Stress, and Insulin Resistance Was Exacerbated in Zinc Deficient Mouse Model

doi:10.1371/journal.pone.0049257

科研成果详情

题名	Diabetes-Induced Hepatic Pathogenic Damage, Inflammation, Oxidative Stress, and Insulin Resistance Was Exacerbated in Zinc Deficient Mouse Model
作者	Zhang, Chi 1,2,3; Lu, Xuemian1; Tan, Yi2,3; Li, Bing 3,4; Miao, Xiao 3,4; Jin, Litai2; Shi, Xue 5; Zhang, Xiang 5; Miao, Lining 4; Li, Xiaokun2; Cai, Lu1,2,3,6
发表日期	2012-12-12
发表期刊	PLOS ONE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	FATTY LIVER-DISEASE ; APOPTOSIS ; ACTIVATION ; PATHWAY ; TPEN ; DEGRADATION ; MORTALITY ; CHELATOR ; DEFENSE ; TYPE-2
摘要	Objectives: Zinc (Zn) deficiency often occurs in the patients with diabetes. Effects of Zn deficiency on diabetes-induced hepatic injury were investigated. Methods: Type 1 diabetes was induced in FVB mice with multiple low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with and without Zn chelator, N,N,N',N'-tetrakis (2-pyridylemethyl) ethylenediamine (TPEN), at 5 mg/kg body-weight daily for 4 months. Hepatic injury was examined by serum alanine aminotransferase (ALT) level and liver histopathological and biochemical changes. Results: Hepatic Zn deficiency (lower than control level, p<0.05) was seen in the mice with either diabetes or TPEN treatment and more evident in the mice with both diabetes and TPEN. Zn deficiency exacerbated hepatic injuries, shown by further increased serum ALT, hepatic lipid accumulation, inflammation, oxidative damage, and endoplasmic reticulum stress-related cell death in Diabetes/TPEN group compared to Diabetes alone. Diabetes/TPEN group also showed a significant decrease in nuclear factor-erythroid 2-related factor 2 (Nrf2) expression and transcription action along with significant increases in Akt negative regulators, decrease in Akt and GSK-3 beta phosphorylation, and increase in nuclear accumulation of Fyn (a Nrf2 negative regulator). In vitro study with HepG2 cells showed that apoptotic effect of TPEN at 0.5-1.0 mu M could be completely prevented by simultaneous Zn supplementation at the dose range of 30-50 mu M. Conclusions: Zn is required for maintaining Akt activation by inhibiting the expression of Akt negative regulators; Akt activation can inhibit Fyn nuclear translocation to export nuclear Nrf2 to cytoplasm for degradation. Zn deficiency significantly enhanced diabetes-induced hepatic injury likely through down-regulation of Nrf2 function.
资助项目	American Diabetes AssociationAmerican Diabetes Association [1-11-BA-17]; Zhejiang Province Extremely Key Subject Building Project; Wenzhou Medical College; National Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81000294]
出版者	PUBLIC LIBRARY SCIENCE
出版地	SAN FRANCISCO
ISSN	1932-6203
卷号	7 期号:12 页码:e49257.
DOI	10.1371/journal.pone.0049257
页数	8
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000313236200012
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	23251339
PMC记录号	PMC3520990
SCOPUSEID	2-s2.0-84871255763
通讯作者地址	[Li, Xiaokun]The Chinese-American Research Institute for Diabetic Complications,The Wenzhou Medical College,China
Scopus学科分类	Multidisciplinary
引用统计	被引频次：72[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/6955
专题	其他_附属第三医院（瑞安市人民医院）温州医科大学
通讯作者	Li, Xiaokun
作者单位	1.Ruian Center of the Chinese-American Research Institute for Diabetic Complications,The Third Affiliated Hospital of the Wenzhou Medical College,China; 2.The Chinese-American Research Institute for Diabetic Complications,The Wenzhou Medical College,China; 3.Kosair Children Hospital Research Institute,Department of Pediatrics of University of Louisville School of Medicine,United States; 4.The Second Hospital of Jilin University,China; 5.Department of Chemistry,University of Louisville,United States; 6.Departments of Pharmacology and Toxicology, and Radiation Oncology,University of Louisville,United States
第一作者单位	其他_附属第三医院（瑞安市人民医院）; 温州医科大学
通讯作者单位	温州医科大学
第一作者的第一单位	其他_附属第三医院（瑞安市人民医院）
推荐引用方式 GB/T 7714	Zhang, Chi,Lu, Xuemian,Tan, Yi,et al. Diabetes-Induced Hepatic Pathogenic Damage, Inflammation, Oxidative Stress, and Insulin Resistance Was Exacerbated in Zinc Deficient Mouse Model[J]. PLOS ONE,2012,7(12):e49257..
APA	Zhang, Chi., Lu, Xuemian., Tan, Yi., Li, Bing., Miao, Xiao., ... & Cai, Lu. (2012). Diabetes-Induced Hepatic Pathogenic Damage, Inflammation, Oxidative Stress, and Insulin Resistance Was Exacerbated in Zinc Deficient Mouse Model. PLOS ONE, 7(12), e49257..
MLA	Zhang, Chi,et al."Diabetes-Induced Hepatic Pathogenic Damage, Inflammation, Oxidative Stress, and Insulin Resistance Was Exacerbated in Zinc Deficient Mouse Model".PLOS ONE 7.12(2012):e49257..