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首页> 外文期刊>American Journal of Physiology >A1 adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents.
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A1 adenosine receptor partial agonist lowers plasma FFA and improves insulin resistance induced by high-fat diet in rodents.

机译：A1腺苷受体部分激动剂可降低啮齿类动物血浆FFA并提高高脂饮食诱导的胰岛素抵抗。

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There is substantial evidence in the literature that elevated plasma free fatty acids (FFA) play a role in the pathogenesis of type 2 diabetes. CVT-3619 is a selective partial A(1) adenosine receptor agonist that inhibits lipolysis and lowers circulating FFA. The present study was undertaken to determine the effect of CVT-3619 on insulin resistance induced by high-fat (HF) diet in rodents. HF diet feeding to rats for 2 wk caused a significant increase in insulin, FFA, and triglyceride (TG) concentrations compared with rats fed chow. CVT-3619 (1 mg/kg) caused a time-dependent decrease in fasting insulin, FFA, and TG concentrations. Acute administration of CVT-3619 significantly lowered the insulin response, whereas glucose response was not different with an oral glucose tolerance test. Treatment with CVT-3619 for 2 wk resulted in significant lowering of FFA, TG, and insulin concentrations in rats on HF diet. To determine the effect of CVT-3619 on insulin sensitivity, hyperinsulinemic euglycemic clamp studies were performed in C57BL/J6 mice fed HF diet for 12 wk. Glucose infusion rate was decreased significantly in HF mice compared with chow-fed mice. CVT-3619 treatment 15 min prior to the clamp study significantly (P < 0.01) increased glucose infusion rate to values similar to that for chow-fed mice. In conclusion, CVT-3619 treatment lowers FFA and TG concentrations and improves insulin sensitivity in rodent models of insulin resistance.
机译：文献中有大量证据表明血浆游离脂肪酸（FFA）升高在2型糖尿病的发病机理中起作用。 CVT-3619是选择性的部分A（1）腺苷受体激动剂，可抑制脂解作用并降低循环FFA。本研究旨在确定CVT-3619对高脂（HF）饮食在啮齿动物中诱导的胰岛素抵抗的影响。与喂普通食物的大鼠相比，喂食高脂饮食2周的高脂饮食导致胰岛素，FFA和甘油三酸酯（TG）浓度显着增加。 CVT-3619（1 mg / kg）导致空腹胰岛素，FFA和TG浓度随时间的下降。急性给予CVT-3619可以显着降低胰岛素反应，而口服葡萄糖耐量试验对葡萄糖反应没有影响。用CVT-3619治疗2周会导致HF饮食大鼠的FFA，TG和胰岛素浓度显着降低。为了确定CVT-3619对胰岛素敏感性的影响，在喂食HF饮食12周的C57BL / J6小鼠中进行了高胰岛素正常血糖钳夹研究。 HF小鼠的葡萄糖输注速率与普通喂养的小鼠相比明显降低。在钳夹研究前15分钟进行CVT-3619治疗，使葡萄糖输注速率显着提高（P <0.01），达到与cho饲小鼠相似的值。总之，在啮齿类胰岛素抵抗模型中，CVT-3619处理可降低FFA和TG浓度并提高胰岛素敏感性。

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