The specific aims of this project are: (1) to search for the primary action and site of action of the diabetic alleles (db and db2J) that cause a disease in mice resembling maturity-onset diabetes mellitus in man; (2) to define the physiology, biochemistry, and histopathology of the disease caused by these two alleles in different genetic backgrounds; (3) to compare the effects of the diabetes alleles with those caused by unrelated genes, such as obese (ob), yellow (Ay, Avy), and fat (fat), which also cause hyperphagia, obesity, hyperinsulinemia, and mild hyperglycemia; and (4) to compare feed efficiencies of mutant with that of normal mice in attempts to evaluate a potential "thrifty genotype" as contributing to the obesity-diabetes syndromes.