SPP1 and Hyperinsulinemia: Although the mechanism of action of OPN in the pancreatic duct epithelium is not clear, some reports have mentioned that hyperglycemia is involved in the proliferation of vascular smooth muscle cells (VSMC) via up-regulation of OPN [24], and it is believed that increased OPN expression is due to hyperglycemia and hyperinsulinemia in the pancreatic duct epithelium, which in turn accelerates cell proliferation.