Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome

doi:10.1096/fj.13-230433

科研成果详情

题名	Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome
作者	Kai，Alan K.L.1; Lam，Amy K.M.1; Chen，Yingxian 1; Tai，Andrew C.P.1; Zhang，Xinmei 2; Lai，Angela K.W.1; Yeung，Patrick K.K.1; Tam，Sidney 3; Wang，Jian 6; Lam，Karen S.2,5; Vanhoutte，Paul M.4,5; Bos，Johannes L.7; Chung，Stephen S.M.8; Xu，Aimin 2,5; Chung，Sookja K.1,5
发表日期	2013-10-01
发表期刊	FASEB Journal
卷号	27 期号:10 页码:4122-4135
摘要	Previously, exchange protein directly activated by cAMP 2 (Epac2) and PKA were known to play a role in glucose-stimulated insulin secretion (GSIS) by pancreatic β cells. The present study shows that Epac1 mRNA is also expressed by β cells. Therefore, we generated mice and embryonic stem (ES) cells with deletion of the Epac1 gene to define its role in β-cell biology and metabolism. The homozygous Epac1-knockout (Epac) mice developed impaired glucose tolerance and GSIS with deranged islet cytoarchitecture, which was confirmed by isolated islets from adult Epac1 mice. Moreover, Epac1 mice developed more severe hyperglycemia with increased β-cell apoptosis and insulitis after multiple low-dose streptozotocin (MLDS; 40 mg/kg) treatment than Epac1 mice. Interestingly, Epac1 mice also showed metabolic defects, including increased respiratory exchange ratio (RER) and plasma triglyceride (TG), and more severe diet-induced obesity with insulin resistance, which may contributed to β-cell dysfunction. However, islets differentiated from Epac ES cells showed insulin secretion defect, reduced Glut2 and PDX-1 expression, and abolished GLP-1-stimulated PCNA induction, suggesting a role of Epac1 in β-cell function. The current study provides in vitro and in vivo evidence that Epac1 has an important role in GSIS of β cells and phenotype resembling metabolic syndrome. © FASEB.
关键词	Glucose transporter type 2 Glucose-stimulated insulin secretion High-fat-diet-induced obesity Hyperglycemia Multiple lowdose streptozotocin-induced diabetes
DOI	10.1096/fj.13-230433
URL	查看来源
语种	英语English
Scopus入藏号	2-s2.0-84885160578
引用统计	被引频次：49[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://repository.uic.edu.cn/handle/39GCC9TT/6536
专题	北师香港浸会大学
通讯作者	Chung，Sookja K.
作者单位	1.Department of Anatomy, Faculty of Medicine, University of Hong Kong,21 Sassoon Rd.,Hong Kong,Hong Kong 2.Department of Medicine, University of Hong Kong,Hong Kong,Hong Kong 3.Clinical Biochemistry Unit, University of Hong Kong,Hong Kong,Hong Kong 4.Department of Pharmacology, University of Hong Kong,Hong Kong,Hong Kong 5.Research Centre of Heart, Brain, Hormone, and Healthy Aging, Li Ka Shing Faculty of Medicine, University of Hong Kong,Hong Kong,Hong Kong 6.Forth Military Medical University,Xi'an,China 7.Molecular Cancer Research, Universitair Medisch Centrum Utrecht,Utrecht,Netherlands 8.Division of Science and Technology, United International College,Zhuhai,China
推荐引用方式 GB/T 7714	Kai，Alan K.L.,Lam，Amy K.M.,Chen，Yingxianet al. Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome[J]. FASEB Journal, 2013, 27(10): 4122-4135.
APA	Kai，Alan K.L., Lam，Amy K.M., Chen，Yingxian., Tai，Andrew C.P., Zhang，Xinmei., .. & Chung，Sookja K. (2013). Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome. FASEB Journal, 27(10), 4122-4135.
MLA	Kai，Alan K.L.,et al."Exchange protein activated by cAMP 1 (Epac1)-deficient mice develop β-cell dysfunction and metabolic syndrome". FASEB Journal 27.10(2013): 4122-4135.