Immune Function in Obese, Diabetic, Hyperinsulinemic C57BL/KsJ-db+/db+ and C57BL/6J-ob/ob Mice
The mutant C57BL/KsJ-db+/db+ (db/db) mouse was first described by Hummel and co-workers of the Jackson Laboratory (Hummel et al., 1966). The mutant diabetes (db) gene is inherited as an autosomal recessive with full penetrance. In the homozygous state, the db gene is associated with a metabolic disturbance closely resembling adultoneset, insulin-independent diabetes mellitus. The diabetic syndrome in db/db mice is characterized by obesity, hyperphagia, polydypsia, polyuria, and marked hyperglycemia (Hummel et al., 1966; Coleman and Hummel, 1967, 1969; Herberg and Coleman, 1977; Coleman 1978, 1982). Adult db/db mice weigh up to 70 g, while age- and sex-matched littermates only weight up to 30 g. On an ad libitum diet, the average daily food intake of mice is approximately twice normal. Blood sugars run between 350 and 650 mg/dl (normal 100–200 mg/dl). During the first 4–6 months of age plasma insulin concentrations are markedly elevated in the range of 300–600 μU/ml. After approximately 6 months of age, plasma insulin concentrations fall to within the normal range of 10–100 µU/ml. Early in the course of the disease, during the period of hyperinsulinemia, the islets of Langerhans are characterized by β cell hypertrophy and hyperplasia with β cell degranulation (Like and Chick 1970). The mice are insulin-resistant and have a decrease in the number of insulin receptors on insulin-sensitive target tissues (Kahn et al., 1973, Chang et al., 1975, Raizada et al., 1980). Later in the disease, concomitant with the drop in plasma insulin concentration, progressive atrophy of islet cells occurs (Like and Chick, 1970).
KeywordsSpleen Cell Suppressor Cell Plasma Insulin Concentration Mixed Lymphocyte Culture Blastogenic Response
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