Targeted expression of islet neogenesis associated protein to beta cells enhances glucose tolerance and confers resistance to streptozotocin-induced hyperglycemia

被引：16

作者：

Chang, Tien-Jyun ^{[1
]}

Weaver, Jessica R. ^{[1
]}

Bowman, Angela ^{[1
]}

Leone, Kendall ^{[1
]}

Raab, Rebekah ^{[1
]}

Vinik, Aaron I. ^{[1
]}

Pittenger, Gary L. ^{[1
]}

Taylor-Fishwick, David A. ^{[1
,2
]}

机构：

[1] Eastern Virginia Med Sch, Strelitz Diabet Ctr, Dept Internal Med, Norfolk, VA 23507 USA

[2] Eastern Virginia Med Sch, Strelitz Diabet Ctr, Dept Microbiol & Mol Cell Biol, Norfolk, VA 23507 USA

来源：

MOLECULAR AND CELLULAR ENDOCRINOLOGY | 2011年 / 335卷 / 02期

关键词：

INGAP; Diabetes; Neogenesis; Insulin sensitivity; Streptozotocin; NADPH oxidase; NADPH OXIDASE; DIABETES-MELLITUS; GENE-EXPRESSION; FAMILY-MEMBER; INGAP; STRESS; INFLAMMATION; DYSFUNCTION; MITOCHONDRIAL; CYTOKINES;

D O I：

10.1016/j.mce.2010.12.026

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Islet neogenesis associated protein (INGAP) stimulates experimental pancreatic islet growth, as evidenced by elevated markers of beta cell mass, in rodents, dogs and primates. Previous analyses of mice that have a transgenic expression of INGAP targeted to the exocrine pancreas have indicated additional biological activity attributed to INGAP. In this study we report on mice with a targeted expression of INGAP to the islet beta cell. The beta cell transgenic mice (IP-INGAP) showed enhanced normalization of blood glucose during IPGTT. Further, IP-INGAP mice had a significant delay in development of hyperglycemia following a diabetogenic dose of streptozotocin. INGAP conferred beta cell protection and enhanced islet function. Analysis of oxidative stress genes in IP-INGAP mice revealed a decrease in islet expression of the NADPH oxidase, NOX1, in both basal state and in response to pro-inflammatory cytokine stimulation. These data are consistent with a pleiotropic role for INGAP and reveal new pathways to target in the discovery of improved diabetic therapies. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

引用

页码：104 / 109

页数：6

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