学科主题基础医学
Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice
Ding, Jun1; Gao, Yan1,2; Zhao, Jing1; Yan, Hong1; Guo, Shi-ying1; Zhang, Qin-xian2; Li, Ling-song3; Gao, Xiang1,2
刊名ENDOCRINOLOGY
2009-05-01
DOI10.1210/en.2008-1006
150期:5页:2136-2144
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]STIMULATED INSULIN-SECRETION ; GLUCOSE-HOMEOSTASIS ; ENERGY-EXPENDITURE ; ISLET DEVELOPMENT ; BODY-WEIGHT ; FOOD-INTAKE ; RECEPTOR ; GLP-1 ; GENE ; PANCREAS
英文摘要

Heterozygosity for the Pax6 allele is associated with impaired glucose tolerance in humans. With a Pax6 mutant mouse model, we found many of the metabolic abnormalities were consistent with the effects of down-regulating the expression of glucagon-like peptide 1 (GLP-1). In addition to impaired glucose tolerance, adult heterozygous mutant mice (Pax6(m/+)) secreted less insulin responding to glucose and arginine administration compared with control mice. Moreover, Pax6(m/+) mice showed increased food intake compared with control mice, although they were resistant to diet-induced fat accumulation. Indeed, levels of circulating GLP-1 and intestinal transcription of Gcg/Proglucagon were dramatically reduced in Pax6(m/+) mice. Mutated Pax6 also failed to activate the Gcg/Proglucagon promoter by in vitro transfection assay. Finally, administering the GLP-1 receptor agonist exendin-4 to Pax6(m/+) mice largely reversed their abnormal food intake, glycemic excursion, and insulin secretion. Our studies suggested that disruption of metabolic homeostasis mainly caused by Pax6 haploinsufficiency was mainly mediated by down-regulation of GLP-1. Administration of exendin-4 may be a useful therapy in humans with a similar mutation. (Endocrinology 150: 2136-2144, 2009)

语种英语
WOS记录号WOS:000265407500015
项目编号2005CB522501 ; 2006BAI23B00 ; 2006CB943503 ; 104088
资助机构Ministry of Science and Technology of China ; Ministry of Education of China
引用统计
被引频次:20[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
版本出版稿
条目标识符http://ir.bjmu.edu.cn/handle/400002259/53244
专题北京大学基础医学院_北京大学干细胞研究中心
作者单位1.Peking Univ, Stem Cell Res Ctr, Beijing 100083, Peoples R China
2.Nanjing Univ, Model Anim Res Ctr, Sch Med, MOE Key Lab Model ANim Dis Res, Nanjing 210061, Peoples R China
3.Zhengzhou Univ, Sch Basic Med, Zhengzhou 450001, Peoples R China
推荐引用方式
GB/T 7714
Ding, Jun,Gao, Yan,Zhao, Jing,et al. Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice[J]. ENDOCRINOLOGY,2009,150(5):2136-2144.
APA Ding, Jun.,Gao, Yan.,Zhao, Jing.,Yan, Hong.,Guo, Shi-ying.,...&Gao, Xiang.(2009).Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice.ENDOCRINOLOGY,150(5),2136-2144.
MLA Ding, Jun,et al."Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice".ENDOCRINOLOGY 150.5(2009):2136-2144.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
Pax6 Haploinsufficie(496KB)期刊论文出版稿开放获取CC BY-NC-SA浏览 请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Ding, Jun]的文章
[Gao, Yan]的文章
[Zhao, Jing]的文章
百度学术
百度学术中相似的文章
[Ding, Jun]的文章
[Gao, Yan]的文章
[Zhao, Jing]的文章
必应学术
必应学术中相似的文章
[Ding, Jun]的文章
[Gao, Yan]的文章
[Zhao, Jing]的文章
相关权益政策
暂无数据
收藏/分享
文件名: Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice.pdf
格式: Adobe PDF
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。