Molecular mechanism of beta cell apoptosis induced by p58 in high glucose medium

Type 2 diabetes is a complex disorder with a strong genetic background.CDC2L2 is one of the susceptibility genes of type 2 diabetes in Chinese Han population in northern area.The relationship between CDC2L2 and type 2 diabetes remains unknown.In this paper,the function and its molecular pathway of p58,a protein coded by CDC2L2,in β cell apoptosis were investigated.INS-1 cells cultured in high glucose(20mmol/L)medium were divided into control,vector control(transfected with pcDNA3.0)and experimental(transfected with pcDNA3.0-HA-p58)groups.Beta cell apoptosis level was detected by Annexin V-FITC/PI double staining assay.The flow cytometry results showed that in high glucose medium(20mmol/L),high expression of p58 increased β cell apoptosis significantly compared with that in blank and vector controls(P0.01,P0.05).Western blot revealed that the expressions of Caspase-3,Bax and cytochrome C in cytoplasm increased significantly(P0.05,P0.01,P0.01),whereas the expression of Bcl-2 decreased significantly(P0.05)in the INS-1 cells with high expression of p58,compared with those in both control groups.However,the Bad and Bik expression levels of INS-1 cells did not show obviously changes compared with those in both controls.The above results suggest that in high glucose condition,p58 may induce INS-1 cell apoptosis through up-regulating the expression of Bax and down-regulating the expression of Bcl-2,since both of them could promote the release of cytochrome C into cytoplasm,and finally activate Caspase-3.These results provide an important basis for the further exploration of the molecular mechanism of β cell apoptosis induced by CDC2L2.