Surfactant protein D regulates Notch activity for secretory cell repair and regeneration to prevent post-acute pancreatitis diabetes

Pancreatic endocrine dysfunction following acute pancreatitis (AP) can lead to glucose intolerance and even diabetes. Surfactant protein D (SP-D), as an immune regulatory molecule, has not yet been clarified whether it participates in the regeneration of pancreatic acinar cells and β-cells by modulating the Notch pathway, thereby improving abnormal glucose metabolism. This study aimed to elucidate the role and mechanism of SP-D in promoting the regeneration of pancreatic secretory cells following AP and preventing post-pancreatitis diabetes by regulating the activity of the Notch pathway. Using wild-type and SP-D gene knockout (SP-D⁻/⁻) mice as models, dynamic observations were made after AP induction by Cerulein. Western blot analysis of pancreatic tissue revealed that in the SP-D⁻/⁻-AP group (DG), the key Notch pathway molecules NICD and Hes1 were persistently upregulated; the expression of acinar cell regeneration marker SOX9 and β-cell precursor differentiation marker NGN3 was reduced, and the recovery of the β-cell function marker insulin was delayed. Glucose metabolism testing revealed that the DG had significantly elevated fasting blood glucose (7.6 ± 0.5 mmol/L) at 30 d and an increased area under the curve in the oral glucose tolerance test. Sustained elevation of serum amylase and insufficient insulin secretion, with a markedly delayed repair process. SP-D promotes the regeneration and functional recovery of pancreatic acinar cells and β-cells by inhibiting the overactivation of the Notch pathway, thereby improving abnormal glucose metabolism following AP.