Adenovirus-mediated adiponectin expression augments skeletal muscle insulin sensitivity in male Wistar rats
Adenovirus-mediated adiponectin expression augments skeletal muscle insulin sensitivity in male Wistar rats
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DOI：
10.2337/diabetes.54.5.1304
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发表时间：
2005-05-01
期刊：
影响因子：
7.7
通讯作者：
Olefsky, JM
中科院分区：
文献类型：
--
作者：
Satoh, H;Nguyen, MTA;Olefsky, JM
在这项研究中，我们研究了长期在体内的影响，脂联素对胰岛素敏感性和葡萄糖代谢过表达的脂联素蛋白在雄性Wistar大鼠静脉注射腺病毒（Adv-Adipo）。病毒感染的肝脏分泌脂联素作为高和低分子量复合物。生理性或超生理性高脂联素血症7天后，动物在葡萄糖耐量和胰岛素耐量试验期间显示出增强的胰岛素敏感性。在次最大和最大胰岛素输注速率（4和25 mU）下进行葡萄糖钳夹研究。kg（-1）（.）min（-1））也证明了Adv-Adipo动物中胰岛素敏感性的增加，胰岛素刺激的葡萄糖处置率增加了20- 67%。相反，胰岛素对肝脏葡萄糖输出和血浆游离脂肪酸水平的抑制作用在Adv-Adipo大鼠中与对照组相比没有增强，这表明肝脏中高水平的脂联素表达可能导致局部脱敏。与钳夹数据一致，AMP激活的蛋白激酶的激活在骨骼肌中显著增强（50%），但在肝脏中没有。一个有趣的发现是，在雄性Wistar大鼠中，AdipoR 1和AdipoR 2的表达水平在骨骼肌中高于肝脏，就像在人类中一样。这些结果表明，长期脂联素治疗增强胰岛素敏感性，并可能作为一种治疗人类胰岛素抵抗。
In this study, we investigated the chronic in vivo effect of adiponectin on insulin sensitivity and glucose metabolism by overexpressing the adiponectin protein in male Wistar rats using intravenous administration of an adenovirus (Adv-Adipo). Virally infected liver secreted adiponectin as high and low molecular weight complexes. After 7 days of physiological or supraphysiological hyper-adiponectinemia, the animals displayed enhanced insulin sensitivity during the glucose tolerance and insulin tolerance tests. Glucose clamp studies performed at submaximal and maximal insulin infusion rates (4 and 25 mU (.) kg(-1) (.) min(-1), respectively) also demonstrated increased insulin sensitivity in Adv-Adipo animals, with the insulin-stimulated glucose disposal rate being increased by 20-67%. In contrast, insulin's effect on the suppression of hepatic glucose output and plasma free fatty acid levels was not enhanced in Adv-Adipo rats compared with controls, suggesting that high levels of adiponectin expression in the liver may lead to a local desensitization. Consistent with the clamp data, the activation of AMP-activated protein kinase was significantly enhanced in skeletal muscle (by 50%) but not in liver. One interesting finding was that in male Wistar rats, both AdipoR1 and AdipoR2 expression levels were higher in skeletal muscle than in liver, as it is the case in humans. These results indicate that chronic adiponectin treatment enhances insulin sensitivity and could serve as a therapy for human insulin resistance.