氯氮平对大鼠脂肪细胞GLUT4的影响

目的:了解氯氮平对大鼠血糖(FPG)、血浆胰岛素(FINS)、胰岛素敏感指数(ISI)及脂肪细胞上葡萄糖转运蛋白(GLUT)4表达的影响。方法:12只雄性SD大鼠随机均分成氯氮平组和空白对照组,分别将氯氮平片按20 mg/(kg.d)剂量溶于生理盐水中给大鼠灌胃,空白对照组直接蒸馏水灌胃,共28 d。在第1,14,28天分别剪尾采血,测FPG、FINS,计算ISI,用Western blot法分别测大鼠脂肪细胞内外膜上GLUT4的含量。结果:第14天时氯氮平组大鼠的FPG水平高于空白对照组(P<0.05),ISI水平略低于空白对照组,但差异无显著性(P>0.05)。灌胃28 d时,氯氮平组的FPG、FINS均高于空白对照组差异有显著性(P<0.05),ISI水平低于对照组且差异有显著性(P<0.05)。氯氮平组大鼠脂肪细胞内外膜上的GLUT4含量均较空白对照组下降,但差异不明显。结论:长期服用氯氮平的大鼠体内产生胰岛素抵抗,外周组织GLUT4的表达降低,氯氮平可能既影响胰岛素的分泌功能又同时减少了外周组织对葡萄糖的吸收利用从而影响了糖代谢的正常进行。

Effects of Clozapine on Glucose Transporter 4 in Adipose Tissue in Rats

Objective: To detect the effect of clozapine on serum FPG,FINS,ISI and expression of glucose transporter 4(GLUT4) in adipose tissue in rats.Methods: Twelve SD rats were randomly assigned into two groups with six in each.The rats in clozapine treated group were intragastrically administrated 20 mg/(kg·d) clozapine and the rats in control group were administrated with normal saline for 28 days.The blood glucose,insulin and ISI were detected at the 1st,14th and 28th day and the GLUT4 in adipose cells was assayed with Western-blot as well.Results: At the 14th day post-administration,the glucose level in clozapine group were higher than that in control group(P<(0.05),) the ISI level in clozapine group was slightly lower than that in control group(P>0.05).At the 28th day,the glucose level and insulin level in clozapine group were higher than that in control group(P<0.05),and the ISI level in clozapine group was lower than that in control group(P<0.05).The GLUT4 in adipose cells in clozapine group was lower than that in control group.Conclusion: Clozapine may disturb glucose metabolism by inhibiting GLUT4 of rats.