Metabolic and underlying causes of diabetes mellitus.

It is emphasized that animal models should be used to study specific genotypic or phenotypic expressions associated with diabetes rather than assuming a single animal model can reflect diverse forms of the human disease. Diabetic and normal animals are reviewed on the basis of their usefulness as models of genetic, viral, and chemically induced diabetes, including the often associated immune phenomena. Characteristics of spontaneously diabetic animals with and without obesity are also described with an emphasis on both genetics and metabolic derangements. Recommendations for future animal experimentation include: more longitudinal studies evaluating the role of sex, prenatal environment, diet, and viral or chemical attack on B-cell function; characterization of the immune phenomena associated with B-cell lesions (and insulitis) in diabetic and immunologically incompetent lines; clarification of relationships between obesity and islet-cell function with emphasis on the role of fuel metabolism, vitamins, and minerals; and, finally, the development of new models with specific genetic aberrations placed in normal or diabetic lines.