Role of immune and non-immune aspects of genetics in different expressions of diabetes in db/db mice

The availability of several animal species with diabetes contributed significantly to the understanding of the pathogenesis of the disease and to the development of novel treatment and prevention strategies. Additional contribution derived from investigation of spontaneous and induced forms of diabetes resembling human IDDM and NIDDM, two entities distinguished by their pathogenic background and their clinical presentation. Among the animal models the db/db mouse, with its autosomal recessive db (diabetes) mutated gene on chromosome 4, is of particular importance for the understanding of the complexity of diabetes, since it displays characteristics of NIDDM during the initial stage of the syndrome and of IDDM during the final stage as a result of B-cell necrosis and islet atrophy. Homozygosity for the db gene in mice is characterized by hyperglycemia and hyperinsulinemia early in the process of diabetes, followed by a stage of insulin deficiency and overt IDDM, although the clinical expression differs according to the different genetic background of the mouse. The increased susceptibility of the db/db mouse to the diabetogenic action of viruses and chemical compounds before overt diabetes appears makes this animal an ideal model to study the mechanisms by which diabetogenic or antidiabetogenic genes interact with other genes and/or environmental factors. Previous reviews described different aspects of diabetes in the db/db mouse,1–3 whereas we focus on the role of genetically determined immune and non-immune mechanisms and describe the effect of environmental factors in inducing different expressions of diabetes in db/db mice.