Background Type 2 diabetes mellitus (T2DM) is a commonly observed complication associated with obesity. The effect of fibroblast growth factor 19 (FGF19), a promising therapeutic agent for metabolic disorders, on pancreatic β cells in obesity-associated T2DM remains poorly understood. Methods Human pancreatic β cells were cultured with high glucose (HG) and palmitic acid (PA), followed by treatment with FGF19. The cell proliferation, apoptosis, and insulin secretion were evaluated by CCK-8, qRT-PCR, ELISA, flow cytometry, and western blotting. The expression of the insulin receptor substrate (IRS)/glucose transporter (GLUT) pathway was evaluated. The interaction between FGF19 and IRS1 was predicted using the STRING database and verified by co-immunoprecipitation and immunofluorescence. The regulatory effects of the IRS1/GLUT4 pathway on human pancreatic β cells were assessed by overexpressing IRS1 and silencing IRS1 and GLUT4. Results HG+PA treatment reduced the human pancreatic β cell proliferation and insulin secretion and promoted cell apoptosis. However, FGF19 treatment restored these alterations and significantly increased the expressions of IRS1, GLUT1, and GLUT4 in the IRS/GLUT pathway. Furthermore, FGF19 and IRS1 were found to interact. IRS1 overexpression partially promoted the proliferation of pancreatic β cells and insulin secretion through GLUT4. Additionally, the silencing of IRS1 or GLUT4 attenuated the therapeutic effects of FGF19. Conclusion In conclusion, FGF19 partly promoted the proliferation and insulin secretion of human pancreatic β cells and inhibited apoptosis by upregulating the IRS1/GLUT4 pathway. These findings establish a theoretical framework for the clinical utilization of FGF19 in the treatment of obesity-associated T2DM.

中文翻译：

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FGF19 通过 IRS1/GLUT4 途径促进人胰腺 β 细胞增殖和胰岛素分泌

背景 2 型糖尿病 (T2DM) 是一种常见的与肥胖相关的并发症。成纤维细胞生长因子 19 (FGF19) 是一种很有前景的代谢性疾病治疗药物，但其对肥胖相关 T2DM 中胰腺 β 细胞的影响仍知之甚少。方法用高糖（HG）和棕榈酸（PA）培养人胰腺β细胞，然后用FGF19处理。通过CCK-8、qRT-PCR、ELISA、流式细胞术和蛋白质印迹评估细胞增殖、凋亡和胰岛素分泌。评估胰岛素受体底物（IRS）/葡萄糖转运蛋白（GLUT）途径的表达。使用 STRING 数据库预测 FGF19 和 IRS1 之间的相互作用，并通过免疫共沉淀和免疫荧光进行验证。通过过表达 IRS1 和沉默 IRS1 和 GLUT4 来评估 IRS1/GLUT4 通路对人胰腺 β 细胞的调节作用。结果HG+PA处理可减少人胰腺β细胞增殖和胰岛素分泌，促进细胞凋亡。然而，FGF19 治疗恢复了这些改变，并显着增加了 IRS/GLUT 通路中 IRS1、GLUT1 和 GLUT4 的表达。此外，还发现 FGF19 和 IRS1 存在相互作用。 IRS1过表达部分通过GLUT4促进胰腺β细胞增殖和胰岛素分泌。此外，IRS1 或 GLUT4 的沉默减弱了 FGF19 的治疗效果。结论 综上所述，FGF19通过上调IRS1/GLUT4通路部分促进人胰腺β细胞增殖和胰岛素分泌，抑制细胞凋亡。这些发现为 FGF19 临床应用治疗肥胖相关 T2DM 建立了理论框架。