Effect Of GLP-1 On B Cell De-defferentiation Induced By High Glucose Via Regulation Of Tcf7l2

Objective:To investigate the role and mechanism of liraglutide,an analogue of glucagon-like peptide 1,on β cell de-defferentiation induced by high glucose.Method:In our study,MIN6 cell was exposed in different concentrations of glucose(25,30,35,40 mmol/L glucose)and liraglutide(100nmol/L).qRT-PCR and western blot were performed to determine the mRNA and protein expression of progenitor like-cell markers(Naong,Ucn3,Neurogenin)and P-cell marker genes(Pdx-1,Mafa,Ins-1).Immunoflurescence was performed to detect the expression of Naong and Pdx-1 in MIN6 cell.Tcf712 expression was down-regulated by against Tcf712 and up-regulated by Tcf712 overexpression lentivirus.The cell was exposed in high glucose and liraglutide(100nmol/L).RT-PCR and western blot were performed to determine the mRNA and protein expression of progenitor like-cell markers and P-cell marker genes.Result:1.Compared with control group,the expression of progenitor like-cell markers(such as Naong,Ucn3)increased and expression of β-cell markers(such as Pdx-1,Mafa)decreased significantly in high glucose group(35mmo1/L).2.GLP-1 might decrease the expression of progenitor like-cell markers and increase expression of P-cell markers.3.GLP-1 might increase the mRNA and protein expression level of Tcf712.4.GLP-1 might increase expression level of progenitor like-cell markers(Naong,Ucn3,Neurogenin3)and decrease expression level of β-cell marker genes(Pdx-1,Mafa,Ins-l)via increased levels of Tcf712 gene.Conclusion:GLP-l suppress βcell de-differentiation induced by high glucose via increased levels of Tcf712 gene.