IGF-1 protects against acute pancreatitis by suppressing NF-κB activation through the β-arrestin1/STAT3 pathway.

Acute pancreatitis (AP) is a prevalent inflammatory condition with an upward trend in incidence in recent years. Recent studies have demonstrated the important role of IGF-1 and β-arrestin-1 in inflammation, but their role in AP remains unexplored. Our study explored the role of IGF-1 in acute pancreatitis (AP) using caerulein-induced AP models in wild-type (WT) and β-arrestin1-knockout (KO) mice treated with IGF-1, picropodophyllotoxin (PPP, an IGF-1R inhibitor), Bay11708 (an NF-κB inhibitor), and the STAT3 inhibitor VI. Caerulein injection induced AP, characterized by elevated serum amylase levels, increased MPO activity, and pancreatic pathology. IGF-1 treatment reduced the severity of AP, whereas PPP worsened it. β-arrestin1 deficiency exacerbated pancreatitis and abolished the protective effect of IGF-1. NF-κB and STAT3 were involved in the protective mechanism of IGF-1 through β-arrestin1 regulation. Inhibiting NF-κB or STAT3 altered the protective effect of IGF-1 in AP. In vitro, the protective effect of IGF-1 against caerulein-induced injury was demonstrated in AR42J cells. This study revealed that IGF-1 protected against AP by suppressing NF-κB activation through the β-arrestin1/STAT3 pathway, providing new insights into the role of IGF-1 in AP and potential therapeutic targets.