Vitamin D alleviates type 2 diabetes by promoting autophagy and inhibiting inflammation via the NLRP3 inflammasome pathway.

We investigated whether vitamin D (VD) alleviates type 2 diabetes mellitus (T2DM) by modulating autophagy and inflammation. In wild-type diabetic mice, VD supplementation significantly improved glucose tolerance, reduced fasting blood glucose, and the HOMA-IR (homeostasis model assessment of insulin resistance) index (P < 0.05). Serum levels of IL-1β, TNF-α, and tissue reactive oxygen species were markedly elevated in T2DM mice but significantly decreased after VD treatment (P < 0.05). Histopathological and ultrastructural analyses revealed that VD preserved pancreatic and kidney tissue integrity and increased autophagic structures. Consistently, VD upregulated Beclin-1 and LC3-II while downregulating IL-1β and NF-κB p65 expression in these tissues (P < 0.05). In contrast, these beneficial effects of VD were largely absent in NLRP3-knockout T2DM mice. Collectively, vitamin D exerts therapeutic effects in T2DM by promoting autophagy and inhibiting inflammation, primarily through the ROS-NLRP3-IL-1β-NF-κB signaling pathway.