Irisin通过肠胰轴免疫通讯改善糖尿病小鼠β细胞功能障碍

肠屏障功能与糖尿病的发展密切相关。糖尿病普遍存在肠屏障受损，改善肠屏障功能，是糖尿病预防的潜在靶点。运动可改善肠道炎症性疾病，且与肠屏障存在相关性，但其确切机制仍不明确。Irisin是一种运动后肌肉产生的细胞因子，研究发现，irisin可激活AMPK通路。而AMPK与肠上皮紧密连接关系密切，紧密连接是肠屏障关键组分。由此，我们假设：irisin可通过与肠上皮相关受体相结合，激活AMPK通路，增强上皮紧密连接，改善肠屏障功能，减少肠源性成分渗漏，改善胰岛炎；此外，irisin也可降低2型糖尿病肠内脂多糖渗漏，降低脂多糖所介导的胰岛巨噬细胞浸润，恢复β细胞功能。希望通过本研究，为糖尿病的早期预防提供新的视角。

Intestinal barrier function is closely related to the development of diabetes. Impaired intestinal barrier is frequently identified in diabetes, while the improvement of intestinal barrier function is a potential target for the prevention of diabetes. Exercise can ameliorate intestinal inflammatory diseases, which can be linked to intestinal barrier, but the exact mechanism is still unknown. Irisin is a cytokine generated by muscle after exercise. Studies have found that irisin can activate the AMPK pathway, and AMPK is closely related to the tight junction of intestinal epithelium, a key component of the intestinal barrier. Therefore, we hypothesized that irisin could bind to the related receptor on the intestinal epithelium and subsequently activate AMPK pathway. Thereafter, it could improve intestinal barrier function by strengthening the epithelial tight junctions, reducing intestinal-derived component leakage and ameliorating insulitis. Moreover, irisin could also reduce the leakage of intestinal lipopolysaccharide in type 2 diabetic patients, reducing lipopolysaccharide-mediated macrophage infiltration in islets and recovering β cell function. It is hoped that this study will provide a novel perspective for the early prevention of diabetes.