Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, Basel, Switzerland, and Department of Biomedicine, University of Basel, Basel, Switzerland.
Deptartment of Pediatric Endocrinology and Diabetology and Children's Research Center, University Children's Hospital, Zurich, Switzerland.
Nat Immunol. 2017 Mar;18(3):283-292. doi: 10.1038/ni.3659. Epub 2017 Jan 16.
The deleterious effect of chronic activation of the IL-1β system on type 2 diabetes and other metabolic diseases is well documented. However, a possible physiological role for IL-1β in glucose metabolism has remained unexplored. Here we found that feeding induced a physiological increase in the number of peritoneal macrophages that secreted IL-1β, in a glucose-dependent manner. Subsequently, IL-1β contributed to the postprandial stimulation of insulin secretion. Accordingly, lack of endogenous IL-1β signaling in mice during refeeding and obesity diminished the concentration of insulin in plasma. IL-1β and insulin increased the uptake of glucose into macrophages, and insulin reinforced a pro-inflammatory pattern via the insulin receptor, glucose metabolism, production of reactive oxygen species, and secretion of IL-1β mediated by the NLRP3 inflammasome. Postprandial inflammation might be limited by normalization of glycemia, since it was prevented by inhibition of the sodium-glucose cotransporter SGLT2. Our findings identify a physiological role for IL-1β and insulin in the regulation of both metabolism and immunity.
IL-1β 系统的慢性激活对 2 型糖尿病和其他代谢疾病的有害影响已有充分的文献记载。然而，IL-1β 在葡萄糖代谢中可能具有的生理作用仍未得到探索。在这里，我们发现进食以葡萄糖依赖的方式诱导了腹膜巨噬细胞分泌 IL-1β 的数量的生理性增加。随后，IL-1β 有助于餐后胰岛素分泌的刺激。因此，在重新进食和肥胖期间缺乏内源性 IL-1β 信号转导会降低血浆中胰岛素的浓度。IL-1β 和胰岛素增加了巨噬细胞对葡萄糖的摄取，并且胰岛素通过胰岛素受体、葡萄糖代谢、活性氧的产生以及 NLRP3 炎性小体介导的 IL-1β 的分泌来加强促炎模式。餐后炎症可能会通过正常化血糖来限制，因为通过抑制钠-葡萄糖共转运蛋白 SGLT2 可以预防它。我们的研究结果确定了 IL-1β 和胰岛素在调节代谢和免疫中的生理作用。
