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学科主题: 基础医学
题名:
Pax6 Haploinsufficiency Causes Abnormal Metabolic Homeostasis by Down-Regulating Glucagon-Like Peptide 1 in Mice
作者: Ding, Jun1; Gao, Yan1,2; Zhao, Jing1; Yan, Hong1; Guo, Shi-ying1; Zhang, Qin-xian2; Li, Ling-song3; Gao, Xiang1,2
刊名: ENDOCRINOLOGY
发表日期: 2009-05-01
DOI: 10.1210/en.2008-1006
卷: 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
所属项目编号: 2005CB522501 ; 2006BAI23B00 ; 2006CB943503 ; 104088
项目资助者: Ministry of Science and Technology of China ; Ministry of Education of China
WOS记录号: WOS:000265407500015
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/53244
Appears in Collections:基础医学院_北京大学干细胞研究中心_期刊论文

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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

Recommended Citation:
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.
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