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学科主题临床医学
Reversal of New-Onset Diabetes through Modulating Inflammation and Stimulating beta-Cell Replication in Nonobese Diabetic Mice by a Dipeptidyl Peptidase IV Inhibitor
Tian, Lei1,2,5; Gao, Jie1,2,6; Hao, Jianqiang1,2; Zhang, Yu1,2; Yi, Huimin1,2,7; O′ Brien, Timothy D.3; Sorenson, Robert4; Luo, Jian8; Guo, Zhiguang1,2
刊名ENDOCRINOLOGY
2010-07-01
DOI10.1210/en.2010-0068
151期:7页:3049-3060
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]REGULATORY T-CELLS ; GLUCOSE-TOLERANCE ; NOD MICE ; IN-VIVO ; AUTOIMMUNE ENCEPHALOMYELITIS ; PROGENITOR CELLS ; ENZYME-ACTIVITY ; SELF-TOLERANCE ; LYMPH-NODES ; CD26
英文摘要

Inhibition of dipeptidyl peptidase IV (DPP-IV) activity by NVP-DPP728, a DPP-IV inhibitor, improves the therapeutic efficacy of glucagon-like peptide-1 (GLP-1). CD26 is a membrane-associated glycoprotein with DPP-IV activity and is expressed on lymphocytes. We investigated the effect of NVP-DPP728 on reversing new-onset diabetes in nonobese diabetic (NOD) mice and modulating the inflammatory response and stimulating beta-cell regeneration. New-onset diabetic NOD mice were treated with NVP-DPP728 for 2, 4, and 6 wk. Blood glucose level was monitored. Regulatory T cells in thymus and secondary lymph nodes, TGF-beta 1 and GLP-1 in plasma, and the insulin content in the pancreas were measured. Immunostaining for insulin and bromodeoxyuridine (BrdU) were performed. The correlation of beta-cell replication with inflammation was determined. In NVP-DPP728-treated NOD mice, diabetes could be reversed in 57, 74, and 73% of mice after 2, 4, and 6 wk treatment, respectively. Insulitis was reduced and the percentage of CD4(+)CD25(+)FoxP3(+) regulatory T cells was increased in treated NOD mice with remission. Plasma TGF-beta 1 and GLP-1, the insulin content, and both insulin(+) and BrdU(+) beta-cells in pancreas were also significantly increased. No significant correlations were found between numbers of both insulin(+) and BrdU(+) beta-cells in islets and beta-cell area or islets with different insulitis score in NOD mice with remission of diabetes. In conclusion, NVP-DPP728 treatment can reverse new-onset diabetes in NOD mice by reducing insulitis, increasing CD4(+)CD25(+)FoxP3(+) regulatory T cells, and stimulating beta-cell replication. beta-Cell replication is not associated with the degree of inflammation in NVP-DPP728-treated NOD mice. (Endocrinology 151: 3049-3060, 2010)

语种英语
WOS记录号WOS:000279049300009
Citation statistics
Cited Times:57[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/62283
Collection北京大学第二临床医学院_肝胆外科
北京大学基础医学院
作者单位1.Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA
2.Univ Minnesota, Schulze Diabet Inst, Minneapolis, MN 55455 USA
3.Univ Minnesota, Dept Vet Populat Med, Minneapolis, MN 55455 USA
4.Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA
5.Guangxi Med Univ, Affiliated Hosp 1, Dept Surg, Nanning 530021, Peoples R China
6.Peking Univ, Dept Hepatobiliary Surg, Peoples Hosp, Beijing 100083, Peoples R China
7.Sun Yat Sen Univ, Affiliated Hosp 3, Dept Surg, Guangzhou 510275, Guangdong, Peoples R China
8.Amgen Inc, San Francisco, CA 94080 USA
Recommended Citation
GB/T 7714
Tian, Lei,Gao, Jie,Hao, Jianqiang,et al. Reversal of New-Onset Diabetes through Modulating Inflammation and Stimulating beta-Cell Replication in Nonobese Diabetic Mice by a Dipeptidyl Peptidase IV Inhibitor[J]. ENDOCRINOLOGY,2010,151(7):3049-3060.
APA Tian, Lei.,Gao, Jie.,Hao, Jianqiang.,Zhang, Yu.,Yi, Huimin.,...&Guo, Zhiguang.(2010).Reversal of New-Onset Diabetes through Modulating Inflammation and Stimulating beta-Cell Replication in Nonobese Diabetic Mice by a Dipeptidyl Peptidase IV Inhibitor.ENDOCRINOLOGY,151(7),3049-3060.
MLA Tian, Lei,et al."Reversal of New-Onset Diabetes through Modulating Inflammation and Stimulating beta-Cell Replication in Nonobese Diabetic Mice by a Dipeptidyl Peptidase IV Inhibitor".ENDOCRINOLOGY 151.7(2010):3049-3060.
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