The insulin-deficient Gcgr−/− mice did not become hyperglycemic or hyperketonemic, and their livers exhibited no increase either in phosphor-cAMP response element-binding protein (p-CREB); a mediator of glucagon action (Altarejos and Montminy, 2011) or in the gluconeogenic enzyme phosphoenolpyruvate carboxykinase, both of which are elevated in uncontrolled diabetes. This evidence concerns the gene INS and diabetes mellitus.