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代谢综合征MSG肥胖大鼠胰岛β 细胞功能紊乱机制的初步研究
引用本文:刘率男,刘泉,申竹芳. 代谢综合征MSG肥胖大鼠胰岛β 细胞功能紊乱机制的初步研究[J]. 药学学报, 2008, 43(11): 1106-1111
作者姓名:刘率男  刘泉  申竹芳
作者单位:中国医学科学院、北京协和医学院药物研究所,北京,100050
摘    要:评价代谢综合征动物模型MSG肥胖大鼠的胰岛β细胞功能,并对其功能紊乱机制进行初步研究。采用高葡萄糖钳夹技术证实肥胖性胰岛素抵抗MSG大鼠存在β细胞功能缺陷,GIR值较正常动物降低33.8%[MSG (23.1±3.2) mg·kg-1·min-1, NOR (34.9±8.4) mg·kg-1·min-1, P<0.05];考察病理与生化指标显示MSG大鼠胰岛β细胞数目减少,胰腺甘油三酯含量、NO含量显著增加,SOD水平、胰腺线粒体中总ATP酶和Na+-K+-ATP酶活性均显著降低。结果提示,肥胖性胰岛素抵抗MSG大鼠具有典型的代谢综合征特征,同时伴有胰岛β细胞功能缺陷。这可能与其肥胖导致的炎症因子增加,机体抗氧化能力及膜结构中ATP酶活性下降有关。

关 键 词:MSG肥胖大鼠  代谢综合征  高葡萄糖钳夹  胰岛β细胞功能  ATP酶活性
收稿时间:2008-07-16

A preliminary study on the mechanism of impaired beta cell function in monosodium glutamate obese rat with insulin resistance
LIU Shuai-nan,LIU Quan,SHEN Zhu-fang. A preliminary study on the mechanism of impaired beta cell function in monosodium glutamate obese rat with insulin resistance[J]. Acta pharmaceutica Sinica, 2008, 43(11): 1106-1111
Authors:LIU Shuai-nan  LIU Quan  SHEN Zhu-fang
Abstract:This study is to evaluate beta cell function and investigate the mechanism of impaired pancreatic islet beta cell function in monosodium glutamate(MSG) obese rat with insulin resistance,an animal model of metabolic syndrome.Insulin tolerance test was used to screen MSG obese rats with insulin resistance.Blood concentrations of glucose,triglyceride,total cholesterol and insulin were determined.Beta cell function was assessed with hyperglycemic clamp technique.The morphological alterations in pancreas and changes of islet beta cell mass were evaluated by hematoxylin-eosin(HE) and Gomori aldehyde fuchsin staining.Lipid,oxidative stress relevant factors,nitric oxide(NO) level and activity of ATPase in pancreas and pancreatic mitochondrial were tested.The MSG obese rats with insulin resistance could be validated as a typical metabolic syndrome animal model possessing increased fasting plasma triglycerides and insulin(P<0.001),markedly decreased weight indices of pancreas and impaired glucose-stimulated insulin secretion.Hematoxylin-eosin(HE) and Gomori aldehyde fuchsin staining showed increased adipocytes and fibroplasia deposition in pancreas and reduced beta cell mass.The increased contents of triglyceride and NO level,the decreased SOD levels and activities of total ATPase ((P<0.001)),Na~ -K~ -ATPase(P<0.001) and Ca~(2 )-Mg~(2 )-ATPase(P<0.01) were observed in pancreas and its mitochondria versus normal rat.The study demonstrates that accumulation of lipids in pancreas could lead to increased systemic indicators of inflammation,such as NO,which may influence the activities of several kinds of ATPase in cell membranes and interfere the ion transport,substance metabolism and energy production in pancreas.Finally the MSG obese rats characterized with metabolic syndrome displayed an impairment of beta cell function.
Keywords:MSG obese rat  metabolic syndrome  hyperglycemic clamp technique  beta cell function  activity of ATPase
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