Consistent with this notion, we report that sustained diabetes remission is not observed when icv FGF1 is given to diabetic mice with genetic impairment of melanocortin signaling (agouti mice, Mc4r−/− mice), nor is it observed when melanocortin signaling is blocked pharmacologically in Lepob/ob mice (by icv infusion of an Mc4r antagonist). This evidence concerns the gene MC4R and diabetes mellitus.