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

**Authors:** Qian Ren, Ling Zhang, Chengpei Ni, Lewen Zhang, Yudie Hu, Min Xiao, Zhengyu Zhou

PMC · DOI: 10.1515/biol-2025-1294 · 2026-03-05

## TL;DR

Vitamin D helps treat type 2 diabetes by boosting cell cleanup and reducing inflammation through a specific immune pathway.

## Contribution

This study reveals a new mechanism by which vitamin D improves type 2 diabetes via autophagy and NLRP3 inflammasome inhibition.

## Key findings

- Vitamin D improved glucose tolerance and reduced insulin resistance in diabetic mice.
- Vitamin D reduced inflammation markers like IL-1β and TNF-α in diabetic mice.
- Vitamin D's benefits were blocked in mice lacking the NLRP3 gene.

## Abstract

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.

## Linked entities

- **Genes:** NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548], BECN1 (beclin 1) [NCBI Gene 8678], Map1lc3a (microtubule-associated protein 1 light chain 3 alpha) [NCBI Gene 362245], IL1B (interleukin 1 beta) [NCBI Gene 3553], TNF (tumor necrosis factor) [NCBI Gene 7124]
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), T2DM (MONDO:0005148)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Becn1 (beclin 1, autophagy related) [NCBI Gene 56208] {aka Atg6}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Il18 (interleukin 18) [NCBI Gene 16173] {aka Igif, Il-18}, IL18 (interleukin 18) [NCBI Gene 3606] {aka IGIF, IL-18, IL-1g, IL1F4}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, Sqstm1 (sequestosome 1) [NCBI Gene 18412] {aka A170, OSF-6, Osi, STAP, STONE14, p62}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Nlrp3 (NLR family, pyrin domain containing 3) [NCBI Gene 216799] {aka AGTAVPRL, AII/AVP, Cias1, FCAS, FCU, MWS}, CASP1 (caspase 1) [NCBI Gene 834] {aka ICE, IL1BC, P45}, NLRP3 (NLR family pyrin domain containing 3) [NCBI Gene 114548] {aka AGTAVPRL, AII, AVP, C1orf7, CIAS1, CLR1.1}, Aim2 (absent in melanoma 2) [NCBI Gene 383619] {aka Gm1313, Ifi210}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Vdr (vitamin D (1,25-dihydroxyvitamin D3) receptor) [NCBI Gene 22337] {aka Nr1i1}, Rela (Rela proto-oncogene, NFKB subunit) [NCBI Gene 19697] {aka p65, p65 NF-kappa B, p65 NFkB}, Casp1 (caspase 1) [NCBI Gene 12362] {aka ICE, Il1bc}, IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, Nlrc4 (NLR family, CARD domain containing 4) [NCBI Gene 268973] {aka 9530011P19Rik, CLAN, CLAN1, CLANA, CLANB, CLANC}, Gapdh (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 14433] {aka Gapd}
- **Diseases:** swelling (MESH:D004487), cardiovascular and chronic kidney diseases (MESH:D051436), DM (MESH:D003920), Pancreas (MESH:D010190), mitochondrial dysfunction (MESH:D028361), inflammation (MESH:D007249), hyperglycemia (MESH:D006943), metabolic disorder (MESH:D008659), VD (MESH:D014808), obesity (MESH:D009765), IR (MESH:D007333), hypertrophy (MESH:D006984), -cell (MESH:D002292), dislocation (MESH:D004204), glucose (MESH:D018149), beta-cell dysfunction (MESH:D007340), T2DM (MESH:D003924)
- **Chemicals:** xylene (MESH:D014992), salt (MESH:D012492), phosphate (MESH:D010710), lead nitrate (MESH:C017461), fat (MESH:D005223), paraffin (MESH:D010232), VD (MESH:D014807), ethanol (MESH:D000431), blood glucose (MESH:D001786), SDS (MESH:D012967), free fatty acids (MESH:D005230), 2',7'-dichlorofluorescein-diacetate (MESH:C029569), STZ (MESH:D013311), vitamin A. (MESH:D014801), water (MESH:D014867), sesame oil (MESH:D012715), acetone (MESH:D000096), vitamin D3 (MESH:D002762), hematoxylin (MESH:D006416), FBG (-), lard (MESH:C029310), H&amp;E (MESH:D006371), formalin (MESH:D005557), glucose (MESH:D005947), ROS (MESH:D017382), eosin (MESH:D004801), glutaraldehyde (MESH:D005976), PBS (MESH:D007854), PVDF (MESH:C024865), sucrose (MESH:D013395), citrate (MESH:D019343)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Glycine max (soybean, species) [taxon 3847], Arachis hypogaea (goober, species) [taxon 3818], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** S0033S, F200S
- **Cell lines:** H002 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_EI31), H203 — Homo sapiens (Human), Sandhoff disease, Finite cell line (CVCL_1Y40), H025 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_EI39), H015 — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_AE34)

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12962641/full.md

---
Source: https://tomesphere.com/paper/PMC12962641