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首页> 外文期刊>Naunyn-Schmiedeberg's Archives of Pharmacology >Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2
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Attenuation of insulin resistance in rats by agmatine: role of SREBP-1c, mTOR and GLUT-2

机译:胍丁胺减轻大鼠胰岛素抵抗:SREBP-1c,mTOR和GLUT-2的作用

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摘要

Insulin resistance is a serious health condition worldwide; however, its exact mechanisms are still unclear. This study investigates agmatine (AGM; an endogenous metabolite of l-arginine) effects on insulin resistance induced by high fructose diet (HFD) in rats and the possible involved mechanisms. Sprague Dawley rats were fed 60 % HFD for 12 weeks, and AGM (10 mg/kg/day, orally) was given from week 9 to 12. AGM significantly reduced HFD-induced elevation in fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR) index and liver glycogen content from 3.44-, 3.62- and 2.07- to 2.59-, 2.78- and 1.3-fold, respectively, compared to the control group, while it increased HFD-induced reduction in glucose tolerance. Additionally, AGM significantly decreased HFD-induced elevation in serum triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol levels from 3.18-, 2.97- and 4.75- to 1.25-, 1.25- and 1.07-fold, respectively, compared to control group. Conversely, AGM had no significant effect on HFD-induced changes in fasting glucose, glycosylated hemoglobin, insulin tolerance and high density lipoprotein cholesterol. Furthermore, AGM significantly reduced HFD-induced elevation in mRNA expression of glucose transporter type-2 (GLUT-2), mammalian target of rapamycin (mTOR) and sterol regulatory element-binding protein-1c (SREBP-1c) without affecting that of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) in the liver. Additionally, AGM enhanced ACh-induced aortic relaxation and attenuated liver steatosis induced by HFD. In conclusion, AGM may have a therapeutic potential in insulin resistance through suppressing SREBP-1c, mTOR and GLUT-2 in liver.
机译:胰岛素抵抗是世界范围内的严重健康状况。但是,其确切机制仍不清楚。这项研究调查了胍丁胺(AGM; L-精氨酸的内源性代谢物)对高果糖饮食(HFD)诱导的大鼠胰岛素抵抗的作用及其可能的机制。 Sprague Dawley大鼠接受60%HFD喂养12周,从第9周到第12周给予AGM(10 mg / kg /天,口服)。AGM显着降低了HFD诱导的空腹胰岛素水平升高,稳态模型评估了胰岛素抵抗(HOMA-IR)指数和肝糖原含量分别比对照组高3.44倍,3.62倍和2.07倍至2.59倍,2.78倍和1.3倍,同时增加了HFD诱导的葡萄糖耐量降低。此外,与对照组相比,AGM显着降低了HFD诱导的血清甘油三酯,低密度脂蛋白胆固醇和极低密度脂蛋白胆固醇水平的升高,分别从3.18-,2.97-和4.75-降低到1.25-,1.25-和1.07倍。 。相反,AGM对HFD诱导的空腹血糖,糖基化血红蛋白,胰岛素耐受性和高密度脂蛋白胆固醇的变化无明显影响。此外,AGM显着降低了HFD诱导的2型葡萄糖转运蛋白(GLUT-2),雷帕霉素的哺乳动物靶标(mTOR)和固醇调节元件结合蛋白1c(SREBP-1c)mRNA表达的升高,而不会影响过氧化物酶体肝脏中的增生激活受体α(PPAR-alpha)。此外,AGM增强了ACh诱导的主动脉舒张并减轻了由HFD诱导的肝脂肪变性。总之,AGM可通过抑制肝脏中的SREBP-1c,mTOR和GLUT-2在胰岛素抵抗中具有治疗潜力。

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