Protector Role of Cx30.2 in Pancreatic ß-Cell against Glucotoxicity-Induced Apoptosis
Por:
Ortega-Cuellar D., González-Sánchez I., Piñón-Zárate G., Cerbón M.A., De la Rosa V., Franco-Juárez Y., Castell-Rodríguez A., Islas L.D., Coronel-Cruz C.
Publicada:
1 ene 2024
Resumen:
Glucotoxicity may exert its deleterious effects on pancreatic ß-cell function via a myriad of mechanisms, leading to impaired insulin secretion and, eventually, type 2 diabetes. ß-cell communication requires gap junction channels to be present among these cells. Gap junctions are constituted by transmembrane proteins of the connexins (Cxs) family. Two Cx genes have been identified in ß cells, Cx36 and Cx30.2. We have found evidence that the glucose concentration on its own is sufficient to regulate Cx30.2 gene expression in mouse islets. In this work, we examine the involvement of the Cx30.2 protein in the survival of ß cells (RIN-m5F). Methods: RIN-m5F cells were cultured in 5 mM D-glucose (normal) or 30 mM D-glucose (high glucose) for 24 h. Cx30.2 siRNAs was used to downregulate Cx30.2 expression. Apoptosis was measured by means of TUNEL, an annexin V staining method, and the cleaved form of the caspase-3 protein was determined using Western blot. Results: High glucose did not induce apoptosis in RIN-m5F ß cells after 24 h; interestingly, high glucose increased the Cx30.2 total protein levels. Moreover, this work found that the downregulation of Cx30.2 expression in high glucose promoted apoptosis in RIN-m5F cells. Conclusion: The data suggest that the upregulation of Cx30.2 protects ß cells from hyperglycemia-induced apoptosis. Furthermore, Cx30.2 may be a promising avenue of therapeutic investigation for the treatment of glucose metabolic disorders. © 2024 by the authors.
Filiaciones:
Ortega-Cuellar D.:
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
González-Sánchez I.:
Departamento de Biología, Facultad de Química, UNAM, Mexico City, 04510, Mexico
Piñón-Zárate G.:
Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico City, 04510, Mexico
Cerbón M.A.:
Departamento de Biología, Facultad de Química, UNAM, Mexico City, 04510, Mexico
De la Rosa V.:
Departamento de Fisiología, Facultad de Medicina, UNAM, Mexico City, 04510, Mexico
Franco-Juárez Y.:
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City, 04530, Mexico
Castell-Rodríguez A.:
Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico City, 04510, Mexico
Islas L.D.:
Departamento de Fisiología, Facultad de Medicina, UNAM, Mexico City, 04510, Mexico
Coronel-Cruz C.:
Departamento de Biología Celular y Tisular, Facultad de Medicina, UNAM, Mexico City, 04510, Mexico
gold, All Open Access; Gold Open Access
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