INS and Hyperinsulinemia: Strikingly, PK-ER;Ins2−/−;Ins1+/− mice (retaining a single copy of Ins1) exhibited reduced insulin levels and PanIN formation when fed a HFD compared with PK-ER;Ins2−/−;Ins1+/+ mice (Zhang et al, 2019), arguing that HFD promotes pancreatic tumorigenesis via induction of hyperinsulinemia.