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[Molecular mechanism of β cell apoptosis induced by p58 in high glucose medium.] [Ariticle in Chinese]

Zhang Jie, LIU Yang, YANG Hong-Wang, XU Hai-Yan, MENG Yan

100005Departments of Physiology and Biomedical Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China

Abstract

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 (20 mmol/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 (20 mmol/L), high expression of p58 increased β cell apoptosis significantly compared with that in blank and vector controls (P<0.01, P<0.05). Western blot revealed that the expressions of Caspase-3, Bax and cytochrome C in cytoplasm increased significantly (P<0.05, P<0.01, P<0.01), whereas the expression of Bcl-2 decreased significantly (P< 0.05) 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.

Key words: type 2 diabetes mellitus; CDC2L2; beta cell; apoptosis

Received: 2009-03-27  Accepted: 2009-05-22

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Citing This Article:

Zhang Jie, LIU Yang, YANG Hong-Wang, XU Hai-Yan, MENG Yan . [Molecular mechanism of β cell apoptosis induced by p58 in high glucose medium.] [Ariticle in Chinese] . Acta Physiol Sin 2009; 61 (4): 379-385 (in Chinese with English abstract).