烟酰胺单核苷酸对RIN-m5f细胞中胰岛素分泌及PDX-1和FoxO1基因表达的影响(英文)  

Effect of nicotinamide mononucleotide on insulin secretion and gene expressions of PDX-1 and FoxO1in RIN-m5f cells

作　　者：盛飞凤[1,2] 任贤 戴幸平[1] 徐潇静[1] 董敏[1] 裴奇[1] 屈健[1] 周智广[4] 周宏灏[1] 刘昭前[1] 

机构地区：[1]中南大学临床药理研究所,遗传药理学湖南省重点实验室,长沙410078 [2]广东省妇幼保健院药剂科,广州510010 [3]上海绿谷制药有限公司,上海201220 [4]中南大学湘雅二医院内分泌科,长沙410011

出　　处：《中南大学学报（医学版）》2011年第10期958-963,共6页Journal of Central South University ：Medical Science

基　　金：supported by the National High-Tech R&D Program of China(“863”Program)(2009AA22704);the National Natural Science Foundation of China(30873089,81173129);the Program for Changjiang Scholars and Innovative Research Team in University(IRT0946);the Open Foundation of Innovative Platform in University of Hunan Province of China(10K078);the Science and Technology Plan Key Grant of Hunan Province of China(2009TP40682);the Fundamental Research Funds for the Central Universities(201023100001)

摘　　要：目的:在细胞水平研究烟酰胺单核苷酸(nicotinamide mononucleotide,NMN)对胰岛素分泌的调节作用及其对与胰岛素分泌相关的重要转录因子胰十二指肠同源盒基因(pancreatic and duodenalhomeobox-1,PDX-1)和分叉头框家族转录因子1(forkhead box-containing protein O-1,FoxO1)基因表达的影响。方法:采用大鼠胰岛素ELISA试剂盒检测RIN-m5f细胞胰岛素分泌水平。用Real-time PCR检测RIN-m5f细胞PDX-1和FoxO1的mRNA表达水平。用Western印迹检测RIN-m5f细胞PDX-1蛋白表达水平。结果:用瑞格列奈10 nmol/L+NMN 100μmol/L处理RIN-m5f细胞48 h,与空白对照及DMSO对照组相比,胰岛素分泌量均显著增高(P<0.05);与NMN 50μmol/L组比较,胰岛素分泌量的增高也有统计学意义(P<0.05)。10,50和100μmol/L的NMN作用RIN-m5f细胞36 h,PDX-1的mRNA表达量均上调(依次为P<0.05,P<0.01,P<0.001)。100μmol/L剂量组与10μmol/L和50μmol/L剂量组比较差异也有统计学意义(P<0.001)。50,100和200μmol/L的NMN作用RIN-m5f细胞36或48 h,PDX-1的蛋白表达量与对照组比较差异无统计学意义(P>0.05)。结论:NMN可以调控RIN-m5f细胞中胰岛素的分泌及PDX-1的mRNA表达水平。Objective To investigate the effect of nicotinamide mononucleotide（NMN） on insulin secretion and gene expressions of pancreatic and duodenal homeobox 1（PDX-1） and forkhead box-containing protein O-1（FoxO1）,which were important transcription factors for insulin secretion.Methods Insulin secretion level in RIN-m5f cells was detected by rat insulin ELISA detection kit.The mRNA expression levels of PDX-1 and FoxO1 in RIN-m5f cells were analyzed by real-time PCR.The protein expression of PDX-1 was measured by Western blot.Results Insulin secretion levels in RIN-m5f cells treated with repaglinide（10 nmol/L） plus NMN（100 μmol/L） was significantly higher than those in the blank control,the DMSO control group,and the NMN（50 μmol/L） treated group（P0.05）.The mRNA expression levels of PDX-1 in RIN-m5f cells treated with NMN（10,50 and 100 μmol/L） for 36 h were significantly higher than those in the control group（P0.05,P0.01,and P0.001,respectively）.There was marked differences in the mRNA expression levels of PDX-1 among different concentrations of NMN（P0.001）,but no significant differences in the mRNA expression level of FoxO1（P0.05）.No significant difference was found in the protein expression levels of PDX-1 in RIN-m5f cells treated by NMN（50,100,and 200 μmol/L） for 36 or 48 h compared with the control group（P0.05）.Conclusion NMN can stimulate insulin secretion and upregulate the mRNA expression of PDX-1 in RIN-m5f cells.

关 键 词：烟酰胺单核苷酸 胰十二指肠同源盒基因 分叉头框家族转录因子1 RIN-m5f 

分 类 号：R965[医药卫生—药理学]