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学科主题: 临床医学
题名:
High-fat diet induces early-onset diabetes in heterozygous Pax6 mutant mice
作者: Chen, Yuanyuan1,2; Feng, Ruopeng1; Wang, Hong1; Wei, Rui1; Yang, Jin1; Wang, Liang1; Wang, Haining1; Zhang, Lin1; Hong, Tian-Pei1; Wen, Jinhua1
关键词: high-fat diet ; pancreatic cells ; Pax6 mutation ; type 2 diabetes
刊名: DIABETES-METABOLISM RESEARCH AND REVIEWS
发表日期: 2014-09-01
DOI: 10.1002/dmrr.2572
卷: 30, 期:6, 页:467-475
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Endocrinology & Metabolism
研究领域[WOS]: Endocrinology & Metabolism
关键词[WOS]: IMPAIRED INSULIN-SECRETION ; BETA-CELL DYSFUNCTION ; GLUCOSE-INTOLERANCE ; KNOCKOUT MICE ; KK MICE ; RESISTANCE ; OBESITY ; GENE ; PANCREAS ; MELLITUS
英文摘要:

BackgroundType 2 diabetes is caused by interactions between genetic and environmental factors. Our previous studies reported that paired box6 mutation heterozygosity (Pax6(m/+)) led to defective proinsulin processing and subsequent abnormal glucose metabolism in mice at 6months of age. However, high-fat diet exposure could be an important incentive for diabetes development. In this study, we aimed to develop a novel diabetic model imitating human type 2 diabetes by exposing Pax6(m/+) mice to high-fat diet and to explore the underlying mechanism of diabetes in this model.

MethodsOver 300 Pax6(m/+) and wild-type male weanling mice were randomly divided into two groups and were fed an high-fat diet or chow diet for 6-10weeks. Blood glucose and glucose tolerance levels were monitored during this period. Body weights, visceral adipose weights, blood lipid profiles and insulin sensitivity (determined with an insulin tolerance test) were used to evaluate obesity and insulin resistance. Proinsulin processing and insulin secretion levels were used to evaluate pancreatic cell function.

ResultsAfter 6weeks of high-fat diet exposure, only the Pax6(m/+) mice showed dramatic postloading hyperglycaemia. These mice exhibited significant high-fat diet-induced visceral obesity and insulin resistance and displayed defective prohormone convertase 1/3 production, an increased proinsulin:total insulin ratio and impaired early-phase insulin secretion, because of the Pax6 mutation. Hyperglycaemia worsened progressively over time with the high-fat diet, and most Pax6(m/+) mice on high-fat diet developed diabetes or impaired glucose tolerance after 10weeks. Furthermore, high-fat diet withdrawal partly improved blood glucose levels in the diabetic mice.

ConclusionsBy combining the Pax6(m/+) genetic background with an high-fat diet environment, we developed a novel diabetic model to mimic human type 2 diabetes. This model is characterized by impaired insulin secretion, caused by the Pax6 mutation, and high-fat diet-induced insulin resistance and therefore provides an ideal tool for research on type 2 diabetes pathogenesis and therapies. Copyright (c) 2014 John Wiley & Sons, Ltd.

语种: 英语
所属项目编号: 2012CB517502 ; 2011CB966203 ; 81070701 ; 81000315 ; 81270858 ; 31171417 ; 31101011 ; 7123234 ; 7142083 ; 20100001110083 ; 20120001120076
项目资助者: Chinese National 973 Programme ; National Natural Sciences Foundation of China ; Natural Science Foundation of Beijing City ; Specialized Research Fund for the Doctoral Programme of Higher Education
WOS记录号: WOS:000341718000004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51751
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Peking Univ Hlth Sci Ctr, Peking Univ Stem Cell Res Ctr, Peking Univ Hosp 3, Dept Endocrinol & Metab, Beijing 100191, Peoples R China
2.Nanjing Med Univ, Dept Biochem & Mol Biol, Jiangsu Prov Key Lab Human Funct Genom, Nanjing, Jiangsu, Peoples R China

Recommended Citation:
Chen, Yuanyuan,Feng, Ruopeng,Wang, Hong,et al. High-fat diet induces early-onset diabetes in heterozygous Pax6 mutant mice[J]. DIABETES-METABOLISM RESEARCH AND REVIEWS,2014,30(6):467-475.
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