Abstract

HighlightsWhat are the main findings?Liraglutide potently reduces STZ-induced islet injury by inhibiting HMGB1 release via GLP-1 receptor activation.Liraglutide suppresses pancreatic TLR4 expression and reduces pro-inflammatory cytokines (IFN-γ, IL-1β, CXCL10) in vivo.What are the implications of the main findings?This study identifies HMGB1 as a key downstream target of GLP-1 receptor signaling in the protection against islet injury.Liraglutide may serve as a potential protective agent for preventing islet damage in conditions such as type 1 diabetes or islet transplantation.It is unknown whether the glucagon-like peptide-1 (GLP-1) receptor agonists have a significant protective effect against acute islet injury. High mobility group box 1 (HMGB1) is a damage-associated molecular pattern (DAMP) molecule released from stressed or injured pancreatic β-cells, which triggers inflammatory responses through toll-like receptor 4 (TLR4) signaling. This study investigated the protective effect and mechanism of liraglutide on acute islet injury induced by low doses of streptozotocin (STZ). The results showed that liraglutide pretreatment preserved the structural integrity of pancreatic islets, improved insulin levels and glucose tolerance, and significantly reduced the incidence of diabetes in STZ-treated mice. Liraglutide was also found to inhibit STZ-induced release of HMGB1 and reduce the expression of TLR4 and inflammatory factors IFN-γ, IL-1β, and CXCL10. Moreover, administration of exogenous HMGB1 or antagonism of the GLP-1 receptor diminished liraglutide’s protective effects. These findings suggest that liraglutide has a strong protective effect on STZ-induced acute islet injury, most likely through the inhibition of HMGB1 release, which provides an experimental basis for the application of liraglutide as a protective agent for acute islet injury.