IR@PKUHSC  > 北京大学第三临床医学院
学科主题临床医学
Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3)
Wen, J. H.2,7; Chen, Y. Y.1,7; Song, S. J.2,7; Ding, J.4,5; Gao, Y.4,5; Hu, Q. K.2,7; Feng, R. P.2,7; Liu, Y. Z.3; Ren, G. C.3; Zhang, C. Y.6; Hong, T. P.1,7; Gao, X.4,5; Li, L. S.2,7
关键词Glucose metabolism PAX6 PC1/3 Proinsulin processing
刊名DIABETOLOGIA
2009-03-01
DOI10.1007/s00125-008-1210-x
52期:3页:504-513
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]BETA-CELL ; GENE ; ANIRIDIA ; MUTATION ; TRANSCRIPTION ; PROGLUCAGON ; PANCREAS ; GLUCAGON ; OBESITY ; MICE
英文摘要

Human patients with aniridia caused by heterozygous PAX6 mutations display abnormal glucose metabolism, but the underlying molecular mechanism is largely unknown. Disturbed islet architecture has been proposed as the reason why mice with complete inactivation of paired box 6 (PAX6) in the pancreas develop diabetes. This is not, however, the case in human aniridia patients with heterozygous PAX6 deficiency and no apparent defects in pancreatic development. We investigated the molecular mechanism underlying the development of abnormal glucose metabolism in these patients.

A human aniridia pedigree with a PAX6 R240Stop mutation was examined for abnormal glucose metabolism using an OGTT. The underlying mechanism was further investigated using Pax6 R266Stop mutant small-eye mice, which also have abnormal glucose metabolism similar to that in PAX6 R240Stop mutation human aniridia patients.

Paired box 6 (PAX6) deficiency, both in aniridia patients with a heterozygous PAX6 R240Stop mutation and in mice with a heterozygous Pax6 R266Stop mutation, causes defective proinsulin processing and abnormal glucose metabolism. PAX6 can bind to the promoter and directly upregulate production of prohormone convertase (PC)1/3, an enzyme essential for conversion of proinsulin to insulin. Pax6 mutations lead to PC1/3 deficiency, resulting in defective proinsulin processing and abnormal glucose metabolism.

This study indicates a novel function for PAX6 in the regulation of proinsulin processing and glucose metabolism via modulation of PC1/3 production. It also provides an insight into the abnormal glucose metabolism caused by heterozygous PAX6 mutations in humans and mice.

语种英语
WOS记录号WOS:000263072600016
项目编号2006AA02A114 ; D07050701350704 ; 2006CB943603 ; 2006CB503905 ; 20070192 ; 7062067 ; 30871251 ; 30225037
资助机构Chinese National 863 Projects ; Beijing Ministry of Science and Technology ; Chinese National 973 Projects ; Ministry of Science and Technology for International Collaboration ; Natural Science Foundation of Beijing ; National Natural Science Foundation of China
引用统计
被引频次:38[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59612
专题北京大学第三临床医学院
作者单位1.Chaoyang Cent Hosp, Ctr Eye, Chaoyang, Liaoning, Peoples R China
2.Peking Univ, Dept Endocrinol & Metab, Hosp 3, Beijing 100191, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Dept Cell Biol, Beijing 100191, Peoples R China
4.Nanjing Univ, Model Anim Res Ctr, Nanjing 210093, Jiangsu, Peoples R China
5.Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
6.Nanjing Univ, Sch Life Sci, Nanjing 210093, Jiangsu, Peoples R China
7.Peking Univ, Stem Cell Res Ctr, China Australian Ctr Excellence Stem Cell Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Wen, J. H.,Chen, Y. Y.,Song, S. J.,et al. Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3)[J]. DIABETOLOGIA,2009,52(3):504-513.
APA Wen, J. H..,Chen, Y. Y..,Song, S. J..,Ding, J..,Gao, Y..,...&Li, L. S..(2009).Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3).DIABETOLOGIA,52(3),504-513.
MLA Wen, J. H.,et al."Paired box 6 (PAX6) regulates glucose metabolism via proinsulin processing mediated by prohormone convertase 1/3 (PC1/3)".DIABETOLOGIA 52.3(2009):504-513.
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