As the most abundant circulating leukocytes in humans, neutrophils are increased in WAT and produce the serine protease neutrophil elastase that cleaves insulin receptor substrate 1 (IRS1), preventing IRS1 from binding to PI3K and leading to insulin resistance,418 and the activation of the PI3K pathway is also important in pancreatic carcinogenesis in obesity and DM. This evidence concerns the gene IRS1 and Insulin resistance.