Investigating the protective effect of zinc supplementation on streptozotocin-induced pancreatic beta-cell damage via the HMGB1/TLR2/MAPK pathway
Iranian Journal of Basic Medical Sciences, cilt.29, sa.7, ss.1020-1026, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 29 Sayı: 7
- Basım Tarihi: 2026
- Doi Numarası: 10.22038/ijbms.2026.92275.19914
- Dergi Adı: Iranian Journal of Basic Medical Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, Index Islamicus, Directory of Open Access Journals, Academic Search Ultimate (EBSCO), Middle East & Africa Database (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest)
- Sayfa Sayıları: ss.1020-1026
- Anahtar Kelimeler: Apoptosis, Diabetes mellitus, HMGB1 protein, Toll-like receptor 2, Zinc
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Objective(s): This study investigated the protective effect of zinc supplementation on insulin release via modulation of the High Mobility Group Box 1 (HMGB1)/Toll-like receptor 2 (TLR2)/mitogenactivated protein kinase (MAPK) signaling pathway in streptozotocin (STZ)-induced pancreatic β-cell injury, a commonly used model of type 1 diabetes. Materials and Methods: Human pancreatic β-cells (1.1B4) were divided into five groups: Control, Diabetes, Diabetes + Zinc, Diabetes + Box A, and Diabetes + Zinc + Box A. Diabetes was induced with STZ (20 mM, four hours, type-1), followed by treatment with zinc (30 μM) and/or Box A (100 ng/l). Cellular oxidative stress, apoptosis, mitochondrial membrane potential (MMP), cell viability, and insulin secretion were measured. Protein expressions of HMGB1, TLR2/4, extracellular signal-regulated kinases 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) were analyzed using western blotting. Results: Zinc supplementation restored MMP and total antioxidant status (TAS), reduced apoptotic cell death, and enhanced TLR2 and ERK1/2 expression suppressed by STZ. Combined zinc and Box A treatment markedly increased insulin secretion under both hypo- and hyperglycemic conditions. Conclusion: Zinc exerts protective effects against STZ-induced β-cell damage, likely through modulation of the HMGB1/TLR2/MAPK axis. These findings highlight the therapeutic potential of zinc supplementation in protecting pancreatic β-cell function in diabetes mellitus.