Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Hongo, Bunkyo, Tokyo, Japan.
Cell Metab. 2012 Apr 4;15(4):518-33. doi: 10.1016/j.cmet.2012.01.023. Epub 2012 Mar 29.
Consumption of foods high in saturated fatty acids (FAs) as well as elevated levels of circulating free FAs are known to be associated with T2D. Though previous studies showed inflammation is crucially involved in the development of insulin resistance, how inflammation contributes to β cell dysfunction has remained unclear. We report here the saturated FA palmitate induces β cell dysfunction in vivo by activating inflammatory processes within islets. Through a combination of in vivo and in vitro studies, we show β cells respond to palmitate via the TLR4/MyD88 pathway and produce chemokines that recruit CD11b(+)Ly-6C(+) M1-type proinflammatory monocytes/macrophages to the islets. Depletion of M1-type cells protected mice from palmitate-induced β cell dysfunction. Islet inflammation also plays an essential role in β cell dysfunction in T2D mouse models. Collectively, these results demonstrate a clear mechanistic link between β cell dysfunction and inflammation mediated at least in part via the FFA-TLR4/MyD88 pathway.
已知食用富含饱和脂肪酸（FAs）的食物以及循环游离 FAs 水平升高与 T2D 有关。尽管先前的研究表明炎症在胰岛素抵抗的发展中起着至关重要的作用，但炎症如何导致β细胞功能障碍仍不清楚。我们在这里报告，饱和 FA 棕榈酸通过激活胰岛内的炎症过程，在体内诱导β细胞功能障碍。通过体内和体外研究的结合，我们表明β细胞通过 TLR4/MyD88 途径对棕榈酸作出反应，并产生趋化因子，将 CD11b(+)Ly-6C(+) M1 型促炎单核细胞/巨噬细胞募集到胰岛。耗尽 M1 型细胞可保护小鼠免受棕榈酸诱导的β细胞功能障碍。胰岛炎症在 T2D 小鼠模型中的β细胞功能障碍中也起着至关重要的作用。总的来说，这些结果表明，β细胞功能障碍与炎症之间存在明确的机制联系，至少部分是通过 FFA-TLR4/MyD88 途径介导的。
