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首页> 美国卫生研究院文献>Experimental Diabetes Research >Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats
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Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats

机译：罗格列酮在大冢长埃文斯德岛肥胖大鼠的脂肪组织-肝轴上引起脂联素介导的胰岛素增敏作用。

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Rosiglitazone is an agonist of peroxisome proliferator-activated receptor- (PPAR-) γ that is principally associated with insulin action. The exact mechanisms underlying its insulin-sensitizing action are still not fully elucidated. It is well known that adiponectin mostly secreted in adipose tissue is an insulin sensitizer. Here, we found that treatment of Otsuka Long-Evans Tokushima Fatty (OLETF) rats with rosiglitazone (3 mg/kg, once daily, by oral gavage for 33 weeks) attenuated the increase in fasting plasma insulin concentrations and the index of the homeostasis model assessment of insulin resistance along with the age growth and glucose concentrations during an oral glucose tolerance test. In addition, the increase in plasma alanine aminotransferase activity, concentrations of fasting plasma nonesterified fatty acids and triglyceride, and hepatic triglyceride content was also suppressed. The hepatic protein expression profile revealed that rosiglitazone increased the downregulated total protein expression of insulin receptor substrate 1 (IRS-1) and IRS-2. Furthermore, the treatment suppressed the upregulated phosphorylation of IRS-1 at Ser307 and IRS-2 at Ser731. The results indicate that rosiglitazone ameliorates hepatic and systemic insulin resistance, hepatic inflammation, and fatty liver. Mechanistically, rosiglitazone suppressed hepatic protein overexpression of both phosphorylated nuclear factor- (NF-) κBp65 and inhibitory-κB kinase-α/β, a transcription factor that primarily regulates chronic inflammatory responses and the upstream NF-κB signal transduction cascades which are necessary for activating NF-κB, respectively. More importantly, rosiglitazone attenuated the decreases in adipose adiponectin mRNA level, plasma adiponectin concentrations, and hepatic protein expression of adiponectin receptor-1 and receptor-2. Thus, we can draw the conclusion that rosiglitazone elicits an adiponectin-mediated insulin-sensitizing action at the adipose tissue-liver axis in obese rats. Our findings may provide new insights into the mechanisms of action of rosiglitazone.
机译：罗格列酮是过氧化物酶体增殖物激活受体-（PPAR-）γ的激动剂，主要与胰岛素作用有关。尚不清楚其胰岛素增敏作用的确切机制。众所周知，大多数在脂肪组织中分泌的脂联素是胰岛素敏化剂。在这里，我们发现用罗格列酮（3μg/ kg，每天一次，经口灌胃持续33周）治疗大冢长埃文斯德岛肥胖（OLETF）大鼠可减轻空腹血浆胰岛素浓度的增加和体内稳态模型的指数口服葡萄糖耐量试验期间评估胰岛素抵抗以及年龄增长和葡萄糖浓度。另外，血浆丙氨酸氨基转移酶活性，空腹血浆非酯化脂肪酸和甘油三酸酯的浓度以及肝甘油三酸酯含量的增加也受到抑制。肝蛋白表达谱显示罗格列酮增加了胰岛素受体底物1（IRS-1）和IRS-2的总蛋白表达下调。此外，该处理抑制了Ser 307 处的IRS-1和Ser 731 处的IRS-2的磷酸化上调。结果表明罗格列酮改善了肝和全身胰岛素抵抗，肝炎症和脂肪肝。从机制上讲，罗格列酮抑制了磷酸化核因子-（NF-）κBp65和抑制性-κB激酶-α/β（主要调节慢性炎症反应的转录因子）和上游NF-κB信号转导级联反应的肝蛋白过表达。分别激活NF-κB。更重要的是，罗格列酮减轻了脂联素mRNA水平，血浆脂联素浓度以及脂联素受体1和2的肝蛋白表达的降低。因此，我们可以得出结论，罗格列酮在肥胖大鼠的脂肪组织-肝轴上引起脂联素介导的胰岛素致敏作用。我们的发现可能为罗格列酮的作用机理提供新的见解。

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