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学科主题: 基础医学
题名:
Hepatic glucokinase activity is the primary defect in alloxan-induced diabetes of mice
作者: Zhang, Xuemei2; Liang, Wenbo2; Mao, Yiqing1; Li, Hui1; Yang, Yang1; Tan, Huanran1
关键词: Alloxan ; Alloxan-induced diabetes ; Diabetes mellitus ; Glucokinase
刊名: BIOMEDICINE & PHARMACOTHERAPY
发表日期: 2009-03-01
DOI: 10.1016/j.biopha.2007.07.006
卷: 63, 期:3, 页:180-186
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Medicine, Research & Experimental ; Pharmacology & Pharmacy
研究领域[WOS]: Research & Experimental Medicine ; Pharmacology & Pharmacy
关键词[WOS]: YOUNG MODY ; BETA-CELLS ; METABOLISM ; MODULATION
英文摘要:

Alloxan is a classical diabetogen which is used to achieve beta-cell destruction and type I diabetes due to its selective cytotoxic effect on pancreatic beta-cells. Although alloxan-induced diabetes is widely used in the laboratory to mimic diabetic pathology and for screening antidiabetic drugs, there has not been any comprehensive research in vivo on its diabetogenicity. In our study, alloxan-induced diabetic mice were generated by a single intravenous injection of alloxan (100 mg/kg). Our data show that these mice possess hyperglycemia, hypoinsulinism and morphological characteristics of impaired pancreas that are consistent with the accepted diabetogenic effects of alloxan. Alloxan is believed to confer its diabetogenic effect by inhibiting pancreatic glucokinase activity, leading to pancreatic beta-cell death. We examined the effects of alloxon on the other major site of glucokinase expression, the liver. Our results show that alloxan treatment led to an 81% reduction in glucokinase immunoreactivity and a greater than 90% reduction in glucokinase enzymatic activity in the liver, suggesting that alloxan′s toxicity is not specific to the pancreas. Given the important role of glucokinase as a glucose sensor, and our findings on the effects of alloxon on liver glucokinase activity we propose that the effects on the liver are the primary contributor to pathogenesis in alloxan-induced diabetes. Alloxan-induced diabetes is thus a multifactor-promoted diabetes model which still could be used to examine the antidiabetic effects of compounds prompting insulin secretion and increasing liver-specific glucokinase activity. Despite alloxan-induced diabetes being inconsistent with the natural pathogenesis of human diabetes, further research on the causes of decreased glucokinase activity will help us to unravel the pathogenesis of diabetes and its complications. (C) 2007 Elsevier Masson SAS. All rights reserved.

语种: 英语
所属项目编号: 2002AA214201 ; 2005AA214200
项目资助者: National High Technology Research and Development Program of China
WOS记录号: WOS:000264354000002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/51898
Appears in Collections:基础医学院_药理学系_期刊论文

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作者单位: 1.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pharmacol, Beijing 100083, Peoples R China
2.Dalian Univ, Dept Pharmacol, Coll Med, Dalian 116622, Peoples R China

Recommended Citation:
Zhang, Xuemei,Liang, Wenbo,Mao, Yiqing,et al. Hepatic glucokinase activity is the primary defect in alloxan-induced diabetes of mice[J]. BIOMEDICINE & PHARMACOTHERAPY,2009,63(3):180-186.
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