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IR@PKUHSC  > 北京大学第二临床医学院  > 肝胆外科  > 期刊论文
学科主题: 临床医学
题名:
Reversal of New-Onset Diabetes through Modulating Inflammation and Stimulating beta-Cell Replication in Nonobese Diabetic Mice by a Dipeptidyl Peptidase IV Inhibitor
作者: 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
发表日期: 2010-07-01
DOI: 10.1210/en.2010-0068
卷: 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
项目资助者: Juvenile Diabetes Research Foundation
WOS记录号: WOS:000279049300009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/62283
Appears in Collections:北京大学第二临床医学院_肝胆外科_期刊论文

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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:
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.
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