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大麻素受体1对肥胖大鼠胰岛素抵抗的影响

Effects of cannabinoid receptor 1 on insulin resistance in obese rats

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【作者】 樊大贝秦贵军余勤贾贺堂马晓君闫晓洁

【Author】 FAN Dabei,QIN Guijun,YU Qin,JIA Hetang,MA Xiaojun,YAN Xiaojie Department of Endocrinology,the First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052

【机构】 郑州大学第一附属医院内分泌科

【摘要】 目的:探讨大麻素受体1(CB1受体)对肥胖大鼠胰岛素抵抗的影响。方法:32只雄性SD大鼠给予高脂鼠饲料喂养8周,制作肥胖大鼠模型。以给予普通鼠饲料喂养的6只大鼠作为正常组。将肥胖大鼠随机分为4组,S(模型组)、AW、W、A组,每组大鼠8只。正常组、模型组腹腔内注射等量生理盐水,W、A、AW组分别腹腔内注射CB1受体激动剂WIN55212-2、CB1受体抑制剂AM251、AM251+WIN55212-2;1次/d。2周后,测定大鼠血胰岛素、胰岛素原、C-肽水平,计算胰岛素原/C-肽、胰岛素原/胰岛素;进行高葡萄糖钳夹实验,计算相关参数,包括第1、2时相胰岛素分泌量(1PH和2PH)、胰岛素最大分泌量(MIS)及稳态葡萄糖输注率(GIR60-90)。结果:注药2周后,与正常组比较,模型组血胰岛素、胰岛素原、C-肽、胰岛素原/C-肽、胰岛素原/胰岛素及2PH、MIS水平升高,1PH及GIR60-90水平下降(P<0.05)。W组上述指标变化方向与模型组相同,但变化幅度大于模型组(P<0.05);A组上述指标变化方向与模型组相反,各指标水平与正常组比较,差异无统计学意义(P>0.05);AW组上述指标水平与模型组比较,差异无统计学意义(P>0.05)。结论:CB1受体激动可加重肥胖大鼠胰岛素抵抗,抑制CB1受体可逆转此效应。

【Abstract】 Aim:To study the effects of cannabinoid receptor 1(CB1)on insulin resistance in obese rats.Methods:32 male SD rats were given high-fat diet for 8 weeks to establish obese rat model,and then were randomly divided into model group,W group,A group and AW group,8 in each group.6 rats were given regular diet for 8 weeks as the normal control.Rats in W,A and AW groups were given CB1 agonist(WIN55212-2),CB1 antagonist(AM251),WIN55212-2+AM251,respectively,and the normal control group and model group were given normal saline.Two weeks later,the serum fasting insulin,proinsulin and C-peptide(C-P)levels were measured,and proinsulin/C-P,proinsulin/insulin were calculated.Then hyperglycemic clamp was performed to evaluate the insulin sensitivity,the insulin secretion in Phase 1(1PH),that in Phase 2(2PH),the maximum insulin secretion(MIS),and steady state glucose infusion rate(GIR60-90)were calculated.Results:Compared with those of the normal control group,the serum fasting insulin,proinsulin,C-P,proinsulin/C-P,proinsulin/insulin,2PH and MIS of model group were higher,and 1PH and GIR60-90were lower(P<0.05).Compared with those of the model group,the serum fasting insulin,proinsulin,C-P,proinsulin/C-P,proinsulin/insulin,2PH and MIS of W group were higher(P<0.05),1PH and GIR60-90of W group were lower(P<0.05).The levels of the indicators mentioned above in A group were similar to those of the normal control group(P>0.05).The levels of the indicators mentioned above in AW group were similar to those of the model group(P>0.05).Conclusion:Agitating CB1 receptor could aggravate obese rats’ insulin resistance.Restraining CB1 receptor could reverse these effectiveness.

【基金】 国家自然科学基金资助项目30650005
  • 【文献出处】 郑州大学学报(医学版) ,Journal of Zhengzhou University(Medical Sciences) , 编辑部邮箱 ,2008年04期
  • 【分类号】R589.2;R587.1
  • 【被引频次】2
  • 【下载频次】221
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