While we were unable to assess the effects of reduced insulin gene dose in males using this model, as Ptf1aCreER;KrasLSL-G12D;Ins1+/-;Ins2-/- males developed hyperglycemia, these studies were the first to directly demonstrate that endogenous hyperinsulinemia contributes to development of any cancer [19]. This evidence concerns the gene FOXM1 and Hyperinsulinemia.