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

Background: Diabetes is a chronic metabolic disorder characterized by persistently elevated levels of blood glucose. Research has demonstrated a close relationship between inflammation and the development of diabetes. Vitamin D has been shown to be significantly associated with type 2 diabetes; however, the mechanisms by which it regulates inflammation during the onset of the disease remain incompletely understood. In this study, we investigated the effect of pyroptosis on pancreatic beta-cell function in diabetes and explored the role of 1,25 (OH)2D3 in type 2 diabetes through the pyroptosis signaling pathway. Methods: In both in vivo and in vitro settings, we established a diabetes model combined with 1,25(OH)2D3 intervention to investigate its impact on insulin secretion levels, the release of inflammatory factors, and the expression levels of pyroptosis-related proteins. Results: In both in vivo and in vitro experiments, we have observed that 1,25(OH)2D3 exhibits anti-inflammatory properties by downregulating the expression levels of pyroptosis-related proteins. Furthermore, it provides protection against pancreatic beta-cell damage caused by type 2 diabetes mellitus (T2DM) and enhances insulin secretion. Inhibition of gasdermin D (GSDMD) expression impedes the progression of cell pyroptosis, reduces the amplification of the inflammatory response, and protects pancreatic cells from injury. Conclusion: We hypothesize that the induction of pancreatic cells through pyroptosis occurs via the classical pathway in T2DM, and propose that 1,25(OH)2D3 may have a beneficial effect on this process. Consequently, 1,25(OH)2D3 could potentially serve as an adjuvant to inhibit the pyroptosis of pancreatic beta cells by targeting the classical signaling pathway, thereby reducing the inflammatory response and alleviating symptoms associated with diabetes.