Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKβ
Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKβ
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DOI：
10.1126/science.1061620
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发表时间：
2001-08-31
期刊：
影响因子：
56.9
通讯作者：
Shoelson, SE
中科院分区：
文献类型：
--
作者：
Yuan, MS;Konstantopoulos, N;Shoelson, SE
我们发现，高剂量的水杨酸盐通过敏化胰岛素信号来逆转肥胖啮齿动物的高血糖、高胰岛素血症和血脂异常。 I kappaB 激酶 β (IKK β) 的激活或过度表达会减弱培养细胞中的胰岛素信号传导，而 IKK β 抑制则可逆转胰岛素抵抗。因此，IKK beta，而不是环氧合酶，似乎是相关的分子靶点。杂合缺失 (Ikk beta (+/-)) 可防止高脂肪喂养期间和肥胖 Lep(ob/ob) 小鼠出现胰岛素抵抗。这些发现表明肥胖和 2 型糖尿病的胰岛素抵抗发病机制中存在炎症过程，并将 IKK β 途径确定为胰岛素增敏的靶点。
We show that high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling. Activation or overexpression of the I kappaB kinase beta (IKK beta) attenuated insulin signaling in cultured cells, whereas IKK beta inhibition reversed insulin resistance. Thus, IKK beta, rather than the cyclooxygenases, appears to be the relevant molecular target. Heterozygous deletion (Ikk beta (+/-)) protected against the development of insulin resistance during high-fat feeding and in obese Lep(ob/ob) mice. These findings implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type 2 diabetes mellitus and identify the IKK beta pathway as a target for insulin sensitization.