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

Abstract

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 β-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 β-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 β cells by targeting the classical signaling pathway, thereby reducing the inflammatory response and alleviating symptoms associated with diabetes.