Hu Xingyun, Liu Shanying, Liu Xiaodan, Zhang Jinglu, Liang Ying, Li Yan
Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Endocrine. 2017 Mar;55(3):754-763. doi: 10.1007/s12020-016-1073-8. Epub 2016 Sep 9.
Dipeptidyl peptidase-4 (CD26), a cell surface glycoprotein, is expressed by a variety of cells. It has been shown that dipeptidyl peptidase-4 (CD26) is involved in T cell activation. Nonetheless, its role in inflammatory effects in islet β cells has not been well investigated. In this study, we used sitagliptin, a classic inhibitor of dipeptidyl peptidase-4 (CD26), to research the effect of dipeptidyl peptidase-4 (CD26) on the activation of NF-κB, the expression of inflammatory cytokines, and cell apoptosis in rat insulinoma cells. Results showed that dipeptidyl peptidase-4 (CD26) was expressed on the surface of rat insulinoma cells. Lipopolysaccharide-induced NF-κB activation and expression of inflammatory cytokines were suppressed by sitagliptin treatment in rat insulinoma cells. Furthermore, sitagliptin treatment reduced cell apoptosis stimulated by lipopolysaccharide. Taken together, this study showed for the first time that sitagliptin suppressed NF-κB activation and inflammatory cytokines expression in rat insulinoma cells, suggesting that the dipeptidyl peptidase-4 inhibitor may exert direct anti-inflammatory effects in islet β cells.
二肽基肽酶-4（CD26）是一种细胞表面糖蛋白，由多种细胞表达。已有研究表明，二肽基肽酶-4（CD26）参与T细胞活化。然而，其在胰岛β细胞炎症效应中的作用尚未得到充分研究。在本研究中，我们使用二肽基肽酶-4（CD26）的经典抑制剂西他列汀，来研究二肽基肽酶-4（CD26）对大鼠胰岛素瘤细胞中核因子κB（NF-κB）活化、炎性细胞因子表达及细胞凋亡的影响。结果显示，大鼠胰岛素瘤细胞表面表达二肽基肽酶-4（CD26）。西他列汀处理可抑制大鼠胰岛素瘤细胞中脂多糖诱导的NF-κB活化及炎性细胞因子表达。此外，西他列汀处理可减少脂多糖刺激引起的细胞凋亡。综上所述，本研究首次表明西他列汀可抑制大鼠胰岛素瘤细胞中的NF-κB活化及炎性细胞因子表达，提示二肽基肽酶-4抑制剂可能在胰岛β细胞中发挥直接的抗炎作用。
