Liraglutide regulates the viability of pancreatic α-cells and pancreatic β-cells through cAMP-PKA signal pathway

Aims: As a glucagon-like peptide-1 receptor agonist, liraglutide could effectively increase insulin secretion from pancreatic beta-cells and suppress glucagon secretion from pancreatic alpha-cells in the treatment of hyperglycemia in type 2 diabetes patients. However, the mechanisms for the different regulation of pancreatic alpha-cells and beta-cells are still unclear. In this study, we mainly explored the different effects of liraglutide on mouse pancreatic a-cell line and beta-cell line in vitro. Main methods: Herein, mouse pancreatic alpha-cell line, alpha-TC1-6, and mouse pancreatic beta-cell line, beta-TC-tet, were used to analyze the biological effects of liraglutide in different concentrations. Cell proliferation, cell apoptosis and cell secretion ability were detected in different groups. Besides, the level of miR-375 and cAMP-PKA signal pathway were further evaluated using qPCR and western blot. Key findings: The results indicated that liraglutide could increase the level of miR-375 and cell apoptosis in pancreatic alpha-cells through inhibiting the cAMP-PKA signal pathway, but activate cAMP-PKA signal pathway in pancreatic beta-cells, and further lead to the down-regulation of miR-375 and improve cell viability. Therefore, the treatment with liraglutide could down-regulate the glucagon secretion ability of alpha-TC1-6 cells, and the insulin secretion ability of beta-TC-tet cells was enhanced with the liraglutide treatment in a dose-dependent manner. Significance: In conclusion, we mainly found that liraglutide could regulate the viability of pancreatic a-cells and pancreatic beta-cells through inhibiting and activating cAMP-PKA signal pathway respectively. The better understanding of the mechanism could help us to develop more novel therapy methods for diabetes in the future.