Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China.
Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China.
Metabolism. 2018 Apr;81:1-12. doi: 10.1016/j.metabol.2017.10.015. Epub 2017 Nov 10.
Bariatric surgery could improve pancreatic beta cell function, thereby leading to the remission of the type 2 diabetes mellitus (T2DM). However, the specific mechanism underlying this phenomenon is yet to be revealed. The aim of this study is to test the hypothesis that Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in infiltrating macrophages plays an important role in the modulation of beta cell function after duodenal-jejunal bypass (DJB) surgery.
DJB and sham surgery were performed in diabetic Sprague-Dawley (SD) rats induced by high-fat diet (HFD) and streptozotocin (STZ). Body weight, food intake, and glucose tolerance test (GTT) were measured at indicated time points. Apoptosis of the beta cells was measured by Terminal deoxynucleotidyl transferase mediated dUTP Nick End Labeling (TUNEL) assay. We also assessed the macrophage content and NLRP3 expression in the rat model. Furthermore, macrophage reconstitution was performed after DJB surgery. Beta cell function and NLRP3 inflammasome pathway were re-evaluated in wild-type macrophage reconstitution group and NLRP3-knockdown macrophage reconstitution group.
DJB surgery group rats displayed rapid and sustained improvement in glucose tolerance. Decreased apoptosis and improved secretion function of the beta cells were observed in DJB surgery group. NLRP3 inflammasome pathway in infiltrating macrophages was also suppressed after DJB surgery. Moreover, diabetic remission acquired by DJB sustained in NLRP3-knockdown macrophage reconstitution group, while extinguished in group reconstituted with wild-type macrophage.
NLRP3 inflammasome deactivation in infiltrating macrophages is involved in marked beta cell function improvement after DJB surgery.
减重手术可以改善胰腺β细胞功能，从而使 2 型糖尿病（T2DM）得到缓解。然而，这一现象的具体机制尚未阐明。本研究旨在验证以下假设：在十二指肠空肠旁路（DJB）手术后，浸润巨噬细胞中的 Nod 样受体家族pyrin 结构域包含 3（NLRP3）炎性小体在调节β细胞功能中发挥重要作用。
通过高脂肪饮食（HFD）和链脲佐菌素（STZ）诱导糖尿病 Sprague-Dawley（SD）大鼠进行 DJB 和假手术。在指定时间点测量体重、食物摄入量和葡萄糖耐量试验（GTT）。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）测定法测量β细胞的凋亡。我们还评估了大鼠模型中的巨噬细胞含量和 NLRP3 表达。此外，在 DJB 手术后进行了巨噬细胞重建。在野生型巨噬细胞重建组和 NLRP3 敲低巨噬细胞重建组中，重新评估了β细胞功能和 NLRP3 炎性小体途径。
DJB 手术组大鼠的葡萄糖耐量迅速且持续改善。DJB 手术组观察到β细胞凋亡减少和分泌功能改善。DJB 手术后，浸润巨噬细胞中的 NLRP3 炎性小体途径也受到抑制。此外，DJB 获得的糖尿病缓解在 NLRP3 敲低巨噬细胞重建组中持续存在，而在重建为野生型巨噬细胞的组中消失。
浸润巨噬细胞中 NLRP3 炎性小体的失活参与了 DJB 手术后β细胞功能的显著改善。
