1,25(OH)2D3 promotes insulin secretion through the classical pyroptosis pathway in vitro and vivo

Abstract Purpose: To study the effect of pyroptosis on pancreatic β cell function in diabetes. And explore whether 1,25(OH) 2 D 3 interferes with the progression of type 2 diabetes through pyroptosis signaling pathway. Methods: We explored the relationship between pyroptosis and diabetes and the role of 1,25(OH) 2 D 3 in this process. In vivo and vitro , we constructing a diabetes model combined with 1,25(OH) 2 D 3 intervention. Detected the insulin secretion level, the release level of inflammatory factors and the expression level of pyroptosis-related proteins. Results: In vivo or vitro , we have found that 1,25(OH) 2 D 3 can reduce the level of inflammation, reduce the occurrence of pyroptosis by reducing the expression levels of pyroptosis-related proteins NF-κB, NLRP3, GSDMD, and caspase-1. It can protect pancreatic β cell from T2DM damage and increase insulin secretion. Inhibiting the expression of GSDMD can hinder the progress of cell pyroptosis, reduce the expansion of inflammatory response and protect pancreatic cells from damage. Conclusion: In the occurrence of T2DM, pancreatic cells are induced by pyroptosis through the classical pathway, resulting in reduced insulin secretion. 1,25(OH) 2 D 3 can be used as a potential adjuvant to inhibit pyroptosis of pancreatic cells through pyroptosis classical signaling pathway, reduce inflammatory response and relieve diabetes symptoms.