Lincpint Affects Beta Cell Dysfunction In Type 2 Diabetes

Objective:Diabetes is chronic disease influencing people health seriously,not only bring physical and mental harm to the individual,also bring economic burden to individual.At present,the incidence of diabetes mellitus presents the trend of rising year by year,including type 2 diabetes for more than 90%,and defect of islet beta cell insulin synthesis and secretion and decrease of beta cell number is an important feature of type 2 diabetes.Maintaining beta cell function is mainly associated with transcription factors.Recently,long non-coding RNA(lncRNA)offers a new way for us.The length of lncRNAs is more than 200nt and don’t have protein-coding capacity.They regulate gene expression at epigenetics,transcription and posttranscription levels.LncRNA play an important role in a variety of biological processes,such as growth and development,cell differentiation and cell apoptosis.Abnormal expression of LncRNA can lead to the occurrence of diseases,including cancer,nervous system diseases,blood system diseases.Recent research suggested that IncRNAs were abnormally expressed in diabetes patients,which showed that lncRNA may be related to the occurrence of diabetes.Lincpint(Trp53 induced transcript)was associated with the growth of mice.Knockout of Lincpint appeared growth restriction.And the role of Lincpint in regulation of adult islet has not yet been reported.The aim of this study was to explore the relationship between Lincpint and the function of beta cells.Methods:The expression of Lincpint was detected in Balb/c mice multiple tissues and islets from db/db mice by real-time RT-PCR.MIN6 cells were incubated in palmitate and Lincpint expression was detected by real-time RT-PCR.MIN6 cells were induced by different glucose concentrations and Lincpint expresson was determined by real-time RT-PCR.Specific small interfering RNA(siRNA)was used to knockdown Lincpint in vitro and vivo.Cells apoptosis,proliferation and insulin biosynthesis were analyzed by MTT,flow cytometry,RIA and western blot techniques.Subsequently,ability of insulin synthesis and secretion in vivo was detected by IPGTT,ELISA and real-time RT-PCR.Nucleocytoplasmic separation and RIP assay were used to prove whether Lincpint could affect islet function through Ezh2.Results:We found that Lincpint is abundantly expressed in mouse pancreas compared to other tissues.It was enriched in islets.Lincpint levels decreased in db/db mice.Palmitate could induced to Lincpint downregulation.Glucose could regulate Lincpint expression.Furthermore,knockdown of Lincpint in vitro increased beta cell apoptosis,decreased insulin synthesis and secretion.At the same time,Insl,Ins2 mRNA levels were decreased and Pdxl,MafA,Glut2 expression were dropped in mRNA and protein levels.Moreover,Lincpint interference group(si-Lincpint)in vivo showed slightly impaired glucose tolerance and decreased insulin secretion in IPGTT.Si-Lincpint group showed reduced expression of MafA,Pdxl and Glut2 in mRNA levels.RIP assay showed that Lincpint could bind Ezh2.Conclusion:This study suggests that Lincpint plays a role in beta cell insulin synthesis,secretion and apoptosis.Lincpint may be involved in beta cell dysfunction,thus offering a new target for the diabetes development of preventive or therapeutic agent.