Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.
Eur J Pharmacol. 2021 May 15;899:174042. doi: 10.1016/j.ejphar.2021.174042. Epub 2021 Mar 18.
Inflammation and oxidative stress are important factors that cause islet β-cell dysfunction. STAT3 is not only a major factor in cell proliferation and differentiation, but also plays an important role in mediating inflammation. As a potent inhibitor of STAT3, the effect of Nifuroxazide (Nifu) on pancreatic islet cells in a high glucose environment has not been reported. In the present study, we used high concentration glucose-induced INS-1 cells to examine the effects of Nifu on high glucose-induced cell function by glucose-stimulated insulin secretion (GSIS). The effects of Nifu on high glucose-induced oxidative stress were recorded by oxidative factors and antioxidant factors. Simultaneously, the effect of Nifu on the inflammatory response, apoptosis, and STAT3/SOCS3 signal pathway were validated by quantitative real-time PCR (qRT-PCR) and Western blot. Our study indicated that Nifu significantly improved cell vitality and insulin secretion of INS-1 cells induced by high glucose. We found Nifu significantly inhibited pro-oxidative factors (ROS, MDA) and promoted anti-oxidative factors (SOD, GSH-PX, CAT). Meanwhile, qRT-PCR and Western blot results showed that inflammatory and apoptosis factors were remarkably inhibited by Nifu. Further research indicated that Nifu clearly suppressed the activation of the STAT3/SOCS3 signaling pathway. In conclusion, Nifu can significantly improve the insulin secretion function, protect oxidative stress injury, and reduce inflammatory response and apoptosis in high glucose-induced INS-1 cells. Therefore, Nifu has a new positive effect on maintaining the normal function of pancreatic islet cells in a high glucose environment and provides new drug candidates for the treatment and prevention of diabetes.
炎症和氧化应激是导致胰岛 β 细胞功能障碍的重要因素。STAT3 不仅是细胞增殖和分化的主要因素，而且在介导炎症反应中也发挥着重要作用。Nifuroxazide（Nifu）作为 STAT3 的有效抑制剂，其在高糖环境下对胰岛细胞的作用尚未见报道。本研究采用高浓度葡萄糖诱导 INS-1 细胞，通过葡萄糖刺激胰岛素分泌（GSIS）实验观察 Nifu 对高糖诱导的胰岛细胞功能的影响。通过氧化应激因子和抗氧化应激因子记录 Nifu 对高糖诱导的氧化应激的影响。同时，通过定量实时 PCR（qRT-PCR）和 Western blot 验证了 Nifu 对炎症反应、细胞凋亡和 STAT3/SOCS3 信号通路的影响。我们的研究表明，Nifu 可显著改善高糖诱导的 INS-1 细胞活力和胰岛素分泌。我们发现 Nifu 可显著抑制促氧化因子（ROS、MDA），促进抗氧化因子（SOD、GSH-PX、CAT）。同时，qRT-PCR 和 Western blot 结果表明，Nifu 可显著抑制炎症和凋亡因子。进一步研究表明，Nifu 可明显抑制 STAT3/SOCS3 信号通路的激活。综上所述，Nifu 可显著改善高糖诱导的 INS-1 细胞胰岛素分泌功能，保护氧化应激损伤，减少炎症反应和细胞凋亡。因此，Nifu 对维持高糖环境下胰岛细胞的正常功能具有新的积极作用，为糖尿病的治疗和预防提供了新的药物候选物。
