In conclusion, this study demonstrated that insulin regulated MMP‐2 gelatinolytic activity via its “metabolic” PI3K/AKT and “mitogenic” ERK1/2 signalling pathways in immortalized human pancreatic ductal cell lines, as well as the synergistic effect of hyperinsulinemia and KRAS mutation in the early stage of pancreatic cancer. This evidence concerns the gene MAPK3 and familial pancreatic carcinoma.