IR@PKUHSC  > 北京大学第三临床医学院
学科主题临床医学
GLP-1 Analog Liraglutide Enhances Proinsulin Processing in Pancreatic beta-Cells via a PKA-Dependent Pathway
Wang, Liang1; Liu, Ye1; Yang, Jin1; Zhao, Hejun1; Ke, Jing1; Tian, Qing1; Zhang, Lin1; Wen, Jinhua2; Wei, Rui1; Hong, Tianpei1,2
刊名ENDOCRINOLOGY
2014-10-01
DOI10.1210/en.2014-1218
155期:10页:3817-3828
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
资助者Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]GLUCAGON-LIKE PEPTIDE-1 ; TYPE-2 DIABETES-MELLITUS ; DISPROPORTIONATELY ELEVATED PROINSULIN ; PEPTIDASE-4 INHIBITOR SITAGLIPTIN ; STIMULATED INSULIN-SECRETION ; PROTEIN-KINASE-A ; GLUCOSE-TOLERANCE ; GLYCEMIC CONTROL ; TRANSLATIONAL CONTROL ; CHINESE POPULATION
英文摘要

Hyperproinsulinemia has gained increasing attention in the development of type 2 diabetes. Clinical studies have demonstrated that glucagon-like peptide-1 (GLP-1)-based therapies significantly decrease plasma proinsulin/insulin ratio in patients with type 2 diabetes. However, the underlying mechanism remains unclear. Prohormone convertase (PC)-1/3 and PC2 are primarily responsible for processing proinsulin to insulin in pancreatic beta-cells. We have recently reported that Pax6 mutation down-regulated PC1/3 and PC2 expression, resulting in defective proinsulin processing in Pax6 heterozygous mutant (Pax6(m/+)) mice. In this study, we investigated whether and how liraglutide, a novel GLP-1 analog, modulated proinsulin processing. Our results showed that liraglutide significantly up-regulated PC1/3 expression and decreased the proinsulin to insulin ratio in both Pax6(m/+) and db/db diabetic mice. In the cultured mouse pancreatic beta-cell line, Min6, liraglutide stimulated PC1/3 and PC2 expression and lowered the proinsulin to insulin ratio in a dose-and time-dependent manner. Moreover, the beneficial effects of liraglutide on PC1/3 and PC2 expression and proinsulin processing were dependent on the GLP-1 receptor-mediated cAMP/protein kinase A signaling pathway. The same mechanism was recapitulated in isolated mouse islets. In conclusion, liraglutide enhanced PC1/3- and PC2-dependent proinsulin processing in pancreatic beta-cells through the activation of the GLP-1 receptor/cAMP/protein kinase A signaling pathway. Our study provides a new mechanism for improvement of pancreatic beta-cell function by the GLP-1-based therapy.

语种英语
所属项目编号2012CB517502 ; 81070701 ; 81000315 ; 81270858 ; 20100001110083 ; 20120001120069 ; 20120001120063 ; 20120001120076
资助者Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education ; Chinese National 973 Program ; National Natural Sciences Foundation of China ; Specialized Research Fund for the Doctoral Program of Higher Education
WOS记录号WOS:000342345000011
引用统计
被引频次:4[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/400002259/66222
专题北京大学第三临床医学院
作者单位1.Peking Univ, Dept Endocrinol & Metab, Hosp 3, Beijing 100191, Peoples R China
2.Peking Univ, Stem Cell Res Ctr, Hlth Sci Ctr, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Wang, Liang,Liu, Ye,Yang, Jin,et al. GLP-1 Analog Liraglutide Enhances Proinsulin Processing in Pancreatic beta-Cells via a PKA-Dependent Pathway[J]. ENDOCRINOLOGY,2014,155(10):3817-3828.
APA Wang, Liang.,Liu, Ye.,Yang, Jin.,Zhao, Hejun.,Ke, Jing.,...&Hong, Tianpei.(2014).GLP-1 Analog Liraglutide Enhances Proinsulin Processing in Pancreatic beta-Cells via a PKA-Dependent Pathway.ENDOCRINOLOGY,155(10),3817-3828.
MLA Wang, Liang,et al."GLP-1 Analog Liraglutide Enhances Proinsulin Processing in Pancreatic beta-Cells via a PKA-Dependent Pathway".ENDOCRINOLOGY 155.10(2014):3817-3828.
条目包含的文件
条目无相关文件。
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
[Wang, Liang]的文章
[Liu, Ye]的文章
[Yang, Jin]的文章
百度学术
百度学术中相似的文章
[Wang, Liang]的文章
[Liu, Ye]的文章
[Yang, Jin]的文章
必应学术
必应学术中相似的文章
[Wang, Liang]的文章
[Liu, Ye]的文章
[Yang, Jin]的文章
相关权益政策
暂无数据
收藏/分享
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。