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

Abstract

Abstract Purpose: To study the effect of pyroptosis on pancreatic β cell function in diabetes. And explore whether 1,25(OH)2D3 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)2D3 in this process. In vivo and vitro, we constructing a diabetes model combined with 1,25(OH)2D3 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)2D3 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)2D3 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.