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[奥曲肽对高脂饮食肥胖大鼠肝脏糖异生的影响]

[Effects of octreotide on liver gluconeogenesis in obesity rats fed a high fat diet].

作者信息

Li Mao, Liu Rui, Wang Xiaoxia, Li Xian, Qiang Ou, Yu Tao, Tang Chengwei

出版信息

Wei Sheng Yan Jiu. 2015 Mar;44(2):270-5.

Abstract

OBJECTIVE

To verify the effects of octreotide on liver gluconeogenesis in high fat diet-induced obesity rat.

METHODS

Male SD rats were randomly assigned to control (n = 16) and high-fat diet group (n = 40). After 24 weeks, obese rats selected from high-fat diet group were placed into obese group (n = 16) and octretide-treated group (n = 16). Rats in the octreotide-treated group were subcutaneously injected with octreotide per 12 h (40 mg/kg body weight) for 8 days. Body lengths, body weight, fasting plasma glucose (FPG), triglyceride (TG), total cholesterol (TC), fasting serum insulin and plasma somatostatin (SST) levels were measured. The Lee' s index and HOMA index were calculated. Expression of glucose-6-phosphatase (G6pase), phosphoenolpyruvate carboxykinase (Pepck) and forkhead box-containing protein 0 subfamily-1 (Foxol) mRNA were measured by RT-PCR. Foxol protein in nuclear and cytoplasm were quantified by western blotting.

RESULTS

Compared with control group, body weight, FPG, TG, TC, insulin and HOMA index in obese group were significantly increased. Octreotide treatment showed obviously reduced levels of the parameters. The plasma SST levels in the obese group tended to decrease compared with that in the control group (P >0. 05), while plasma SST levels was increased in the octreotide-treated group compared with that in the obese group (P <0. 05). Obese rats display more G6pase, Pepck and Foxol mRNA and higher ratio of nuclear Foxol protein to cytoplasm Foxol protein than control rats (P < 0. 01), whereas octreotide intervention reversed those changes (P <0. 01).

CONCLUSION

The administration of octreotide can ameliorate abnormal enhancement of hepatic gluconeogenesis, which might be attributed to the reduced activity and expression of Foxol and then decreased expression levels of G6pase and Pepck mRNA.

摘要

目的

验证奥曲肽对高脂饮食诱导的肥胖大鼠肝脏糖异生的影响。

方法

雄性SD大鼠随机分为对照组(n = 16)和高脂饮食组(n = 40)。24周后,从高脂饮食组中选取肥胖大鼠分为肥胖组(n = 16)和奥曲肽治疗组(n = 16)。奥曲肽治疗组大鼠每12小时皮下注射奥曲肽(40 mg/kg体重),共8天。测量大鼠体长、体重、空腹血糖(FPG)、甘油三酯(TG)、总胆固醇(TC)、空腹血清胰岛素和血浆生长抑素(SST)水平。计算李氏指数和HOMA指数。通过RT-PCR检测葡萄糖-6-磷酸酶(G6pase)、磷酸烯醇式丙酮酸羧激酶(Pepck)和含叉头框蛋白0亚家族-1(Foxol)mRNA的表达。通过蛋白质免疫印迹法定量细胞核和细胞质中的Foxol蛋白。

结果

与对照组相比,肥胖组大鼠体重、FPG、TG、TC、胰岛素和HOMA指数显著升高。奥曲肽治疗使这些参数水平明显降低。肥胖组血浆SST水平与对照组相比有降低趋势(P>0.05),而奥曲肽治疗组血浆SST水平与肥胖组相比升高(P<0.05)。肥胖大鼠比对照大鼠表现出更多的G6pase、Pepck和Foxol mRNA以及更高的细胞核Foxol蛋白与细胞质Foxol蛋白比例(P<0.01),而奥曲肽干预逆转了这些变化(P<0.01)。

结论

奥曲肽给药可改善肝脏糖异生的异常增强,这可能归因于Foxol活性和表达降低,进而导致G6pase和Pepck mRNA表达水平降低。

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