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学科主题基础医学
Hepatic glucokinase activity is the primary defect in alloxan-induced diabetes of mice
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
2009-03-01
DOI10.1016/j.biopha.2007.07.006
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
WOS记录号WOS:000264354000002
项目编号2002AA214201 ; 2005AA214200
资助机构National High Technology Research and Development Program of China
引用统计
被引频次:28[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51898
专题北京大学基础医学院_药理学系
北京大学基础医学院
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
推荐引用方式
GB/T 7714
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.
APA Zhang, Xuemei,Liang, Wenbo,Mao, Yiqing,Li, Hui,Yang, Yang,&Tan, Huanran.(2009).Hepatic glucokinase activity is the primary defect in alloxan-induced diabetes of mice.BIOMEDICINE & PHARMACOTHERAPY,63(3),180-186.
MLA Zhang, Xuemei,et al."Hepatic glucokinase activity is the primary defect in alloxan-induced diabetes of mice".BIOMEDICINE & PHARMACOTHERAPY 63.3(2009):180-186.
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