To directly test whether obesity-induced hyperinsulinemia enhances pancreatic tumorigenesis, the Johnson and Kopp groups lowered insulin gene dosage in Ptf1aCreERT;KrasLoxP-STOP-LoxP-G12D (PK-ER) mice, allowing acinar cell-specific activation of oncogenic Kras. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.