Lin Hua V, Kim Ja-Young, Pocai Alessandro, Rossetti Luciano, Shapiro Lawrence, Scherer Philipp E, Accili Domenico
Department of Medicine, Columbia University, New York, NY 10032, USA.
Diabetes. 2007 Aug;56(8):1969-76. doi: 10.2337/db07-0127. Epub 2007 May 2.
Adiponectin increases insulin sensitivity and contributes to insulin's indirect effects on hepatic glucose production.
To examine adiponectin's contribution to insulin action, we analyzed adiponectin levels and activation of AMP-activated protein kinase (AMPK) in insulin receptor transgenic/knockout mice (L1), a genetic model of resistance to insulin's indirect effects on hepatic glucose production.
In euglycemic, insulin-resistant L1 mice, we detected hyperadiponectinemia with normal levels of adiponectin receptor-1 and -2. Moreover, adiponectin administration is unable to lower glucose levels or induce activation of AMPK, consistent with a state of adiponectin resistance. In a subset of hyperglycemic L1 mice, we observed decreased mRNA expression of AdipoR2 in liver and muscle, as well as decreased peroxisome proliferator-activated receptor (PPAR)alpha target gene expression in liver, raising the possibility that deterioration of adiponectin/AdipoR2 signaling via PPARalpha activation contributes to the progression from compensated insulin resistance to diabetes. In contrast, we failed to detect changes in other markers of the systemic or local inflammatory response.
These data provide evidence for a mechanism of adiponectin resistance and corroborate the notion that adiponectin potentiates hepatic insulin sensitivity.
脂联素可提高胰岛素敏感性，并有助于胰岛素对肝脏葡萄糖生成产生间接作用。
为了研究脂联素对胰岛素作用的贡献，我们分析了胰岛素受体转基因/敲除小鼠（L1）（一种对胰岛素对肝脏葡萄糖生成的间接作用产生抵抗的遗传模型）中的脂联素水平以及AMP激活的蛋白激酶（AMPK）的激活情况。
在血糖正常的胰岛素抵抗L1小鼠中，我们检测到脂联素血症升高，而脂联素受体-1和-2水平正常。此外，给予脂联素无法降低血糖水平或诱导AMPK激活，这与脂联素抵抗状态一致。在一部分高血糖L1小鼠中，我们观察到肝脏和肌肉中AdipoR2的mRNA表达降低，以及肝脏中过氧化物酶体增殖物激活受体（PPAR）α靶基因表达降低，这增加了通过PPARα激活导致脂联素/AdipoR2信号转导恶化促成从代偿性胰岛素抵抗发展为糖尿病的可能性。相比之下，我们未检测到全身或局部炎症反应的其他标志物发生变化。
这些数据为脂联素抵抗机制提供了证据，并证实了脂联素增强肝脏胰岛素敏感性这一观点。
