Insulin promotes proliferation of pancreatic ductal epithelial cells by increasing expression of PLK1 through PI3K/AKT and NF-κB pathway.

Pancreatic cancer has a poor prognosis. Many epidemiological evidence show that diabetes is closely related to the occurrence of pancreatic cancer. The concentration of insulin in pancreas local tissues is higher than that in systemic circulation. In this study, we aimed to investigate the effect of insulin on pancreatic duct epithelial cells and identify the potential mechanisms. We found that insulin promoted the proliferation of pancreatic duct epithelial cells in the dependent of increased PLK1. Furthermore, PI3K/AKT and NF-κB pathway were involved in this process. By using PI3K/AKT inhibitor LY294002 and NF-κB shRNA, the increased PLK1 was reversed and cells proliferation was inhibited. Additionally, immunofluorescence analysis revealed the co-localization between PLK1 and β-catenin. We showed that insulin can promote the increased expression of β-catenin dependent on PLK1. This study showed that insulin may promotes cell proliferative vitality of pancreatic ductal epithelial cells by inducing PLK1 through PI3K/AKT and NF-κB pathway; The upregulation of PLK1 may reduce the degradation of β-catenin. This may be one of the mechanisms by which T2DM promotes pancreatic cancer.