西格列汀在胰岛β细胞去分化中的作用研究  

Effect of Sitagliptin on IsletβCell Dedifferentiation

作　　者：王全胜[1] 孙仲侃 欧瑜[2] WANG Quansheng;SUN Zhongkan;OU Yu(Department of Endocrinology,the Afiliated BenQ Hospital of Nanjing Medical Universtiy,Nanjing 21009,China;College of Life Sciences and Technology,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]南京医科大学附属明基医院内分泌科,江苏南京210021 [2]中国药科大学生命科学与技术学院,江苏南京210009

出　　处：《药物生物技术》2024年第6期612-618,共7页Pharmaceutical Biotechnology

基　　金：南京市卫生科技发展专项资金项目(No.YKK21253)。

摘　　要：使用大鼠胰岛β瘤细胞株Rin-m5f建立体外胰岛β细胞去分化模型,探究DPP-4抑制剂西格列汀在胰岛β细胞去分化中的作用。使用葡萄糖或棕榈酸分别诱导胰岛β细胞Rin-m5f去分化,考察血清、葡萄糖和棕榈酸浓度对Rin-m5f存活率的影响,以及葡萄糖浓度和棕榈酸作用时间对去分化相关标志物蛋白及mRNA表达水平的影响,以确定合适的造模条件。考察西格列汀对Rin-m5f细胞存活率的影响,以确定合适的作用浓度。最后,考察不同浓度西格列汀对两种Rin-m5f去分化模型的β细胞标志物及内分泌祖细胞标志物蛋白表达水平的影响。使用10 mg/mL的葡萄糖作用72 h或0.4 mmol/L的棕榈酸作用48 h均能诱导胰岛β细胞Rin-m5f去分化。使用不同浓度的西格列汀干预24 h后,50和100μmol/L的西格列汀可以显著上调两种模型中下调的胰岛β细胞标志物蛋白表达水平,包括PDX-1、MAFA、FOXO1等,且可以降低模型中上调的内分泌祖细胞标志物蛋白表达水平,包括NGN3、OCT4、SOX9等。西格列汀对去分化的胰岛β细胞Rin-m5f具有逆转作用。To investigate the role of DPP-4 inhibitor sitagliptin in isletβcell dedifferentiation by establishing an in vitro rat isletβcell line Rin-m5f dedifferentiation model,glucose or palmitic acid were used to induce isletβcell Rin-m5f dedifferentiation,respectively.The effects of serum,glucose and palmitic acid concentrations on the survival of Rin-m5f,and the effects of glucose concentration and duration of palmitic acid exposure on the protein and mRNA expression levels of dedifferentiation related markers were investigated to determine the optimal modeling conditions.The effect of sitagliptin on the survival of Rin-m5f was investigated to determine the appropriate concentration of drug intervention.Finally,the effects of different concentrations of sitagliptin on the expression levels ofβcell markers and endocrine progenitor cell markers in two models of Rin-m5f dedfferentiation were investigated.Dedifferentiation of isletβcell Rin-m5f could be induced by 10 mg/mL glucose for 72 h or 0.4 mmol/L palmitic acid for 48 h.After 24 h treatment with different concentrations of sitagliptin,50μmol/L and 100μmol/L sitagliptin could significantly up-regulate the down-regulated expression of isletβcell markers in the two models,including PDX-1,MAFA,FOXO1,etc.,and reduce the up-regulated expression of endocrine progenitor cell markers in the models,including NGN3,OCT4,SOX9,etc.Sitagliptin has a reversing effect on dedifferentiated isletβcell Rin-m5f.

关 键 词：DPP-4抑制剂 西格列汀 胰岛β细胞去分化 2型糖尿病 胰岛β细胞标志物 内分泌祖细胞标志物 

分 类 号：R587.1[医药卫生—内分泌]