Investigating the protective effect of zinc supplementation on streptozotocin-induced pancreatic beta-cell damage via the HMGB1/TLR2/MAPK pathway
نویسندگان
1 Faculty of Hamidiye Health Sciences, Department of Nutrition and Dietetics, University of Health Sciences, Istanbul, Türkiye
2 Faculty of Medicine, Department of Physiology, Adiyaman University, Adiyaman, Türkiye
3 Faculty of Health Sciences, Department of Nutrition and Dietetics, Demiroglu Bilim University, Istanbul, Türkiye
doi
10.22038/ijbms.2026.92275.19914چکیده
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)/mitogen-activated protein kinase (MAPK) signaling pathway in streptozotocin (STZ)-induced pancreatic β-cell injury, a commonly used model of type 1 diabetes.Materials and Methos: 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.
