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槟榔碱改善2型糖尿病大鼠糖、脂代谢紊乱
引用本文:姚起鑫,亓竹青,王光,张伟,周寿红,凌宏艳,胡弼.槟榔碱改善2型糖尿病大鼠糖、脂代谢紊乱[J].中国药理学通报,2009,25(11).
作者姓名:姚起鑫  亓竹青  王光  张伟  周寿红  凌宏艳  胡弼
作者单位:1. 南华大学医学院生理学教研室,湖南,衡阳421001;南华大学药物药理研究所,湖南,衡阳421001
2. 南华大学医学院生理学教研室,湖南,衡阳421001
基金项目:湖南省科学技术厅研究项目 
摘    要:目的研究槟榔碱(arecoline)对2型糖尿病大鼠糖、脂代谢的影响及其降糖机制。方法采用高果糖高脂饲料喂养建立2型糖尿病大鼠模型。实验大鼠随机分7组:普通饲料对照组(control),高果糖高脂饲料模型组(HF),高果糖高脂饲料+不同剂量槟榔碱组(1、5、10、20、50mg·kg-1)。观察槟榔碱对糖尿病大鼠血糖、血脂、肝功能及肝脏组织学的影响,采用逆转录-聚合酶链反应(RT-PCR)检测槟榔碱对糖异生酶磷酸烯醇式丙酮酸羧激酶(PEPCK)、葡萄糖-6-磷酸酶(G6Pase)和翼螺旋转录因子O1(FoxO1)、过氧化物酶体增殖物激活受体γ辅激活因子1α(PGC-1α)的mRNA表达的影响。结果与高果糖高脂模型组相比,槟榔碱以剂量依赖的方式降低2型糖尿病大鼠空腹血糖及甘油三脂水平,但是10、20、50mg·kg-1剂量组具有明显肝脏毒性;5mg·kg-1的槟榔碱明显降低糖异生酶PEPCK和G6Pase,转录因子FoxO1及其辅助因子PGC-1α的mRNA的表达。结论低剂量槟榔碱能够改善2型糖尿病大鼠糖脂代谢紊乱,降糖机制为抑制肝脏过度糖异生。

关 键 词:槟榔碱  糖异生  2型糖尿病  胰岛素抵抗  动物模型  高果糖高脂饲料  FoxO1  PGC-1α

Arecoline improved glucose and lipid metabolism in type 2 diabetic rats
Abstract:Aim To investigate the effects of arecoline on glucose and lipid metabolism in type 2 diabetic rats and its mechanisms in glucose metabolism.Methods A type 2 diabetic rat model was established by fed with high fructose-high fat diet.The animals were randomly divided into 7 groups: control group,high fructose-high fat diet group(HF)and high fructose-high fat diet+arecoline(1 mg·kg-1,5 mg·kg-1,10 mg·kg-1,20 mg·kg-1,50 mg·kg-1)groups.The blood glucose,lipid level,hepatic function and liver histology were measured.The mRNA expression of liver glucose-6-phosphatase(G6Pase),phosphoenolpyruvate carboxykinase(PEPCK),Forkhead Box O1(FoxO1)and peroxisome proliferator-activated receptor-γ coactlvator-1α (PGC-1α)were observed through RT-PCR.Results In comparison with the high fructose-high fat diet group,the fasting blood glucose and TC of the rats were significantly decreased by arecoline in a dose-dependment manner in high fructose-high fat diet+arecoline group.But hepatic function was damaged by 10 mg·kg-1,20 mg·kg-1 and 50 mg·kg-1 arecoline.The mRNA expression of hepatic G6Pase,PEPCK,FoxO1 and PGC-1α was decreased by treatment with 1 mg·kg-1 and 5 mg·kg-1 arecoline compared with the high fructose-high fat diet group.Conclusions Low dose arecoline can decrease fasting blood glucose and TC in type 2 diabettic rats,and the mechanism in glucose metabolism may be related to its effect on the inhibition of hepatic gluconeogenesis.
Keywords:FoxO1
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