Investigating the protective effect of zinc supplementation on streptozotocin-induced pancreatic beta-cell damage via the HMGB۱/TLR۲/MAPK pathway

Objective(s): This study investigated the protective effect of zinc supplementation on insulin release via modulation of the High Mobility Group Box ۱ (HMGB۱)/Toll-like receptor ۲ (TLR۲)/mitogen-activated protein kinase (MAPK) signaling pathway in streptozotocin (STZ)-induced pancreatic β-cell injury, a commonly used model of type ۱ diabetes.Materials and Methos: Human pancreatic β-cells (۱.۱B۴) were divided into five groups: Control, Diabetes, Diabetes + Zinc, Diabetes + Box A, and Diabetes + Zinc + Box A. Diabetes was induced with STZ (۲۰ mM, four hours, type-۱), followed by treatment with zinc (۳۰ μM) and/or Box A (۱۰۰ ng/l). Cellular oxidative stress, apoptosis, mitochondrial membrane potential (MMP), cell viability, and insulin secretion were measured. Protein expressions of HMGB۱, TLR۲/۴, extracellular signal-regulated kinases ۱/۲ (ERK۱/۲), 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 TLR۲ and ERK۱/۲ 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 HMGB۱/TLR۲/MAPK axis. These findings highlight the therapeutic potential of zinc supplementation in protecting pancreatic β-cell function in diabetes mellitus.

کلیدواژه ها:

Apoptosis ، Diabetes Mellitus ، HMGB۱ protein ، Toll-like receptor ۲ ، zinc