Hyperinsulinemia in pre-weaning diabetes (db) mice

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Two new strains of diabetes mice (C57BL/ KsJ-m db and C57BL/6J-m db) have been developed with diabetes (db) and the closely linked misty (m) gene coupled on the same chromosome. This permits identification of diabetes mice (m db/m db) by their gray coat color and white feet as early as age 4 days, well before obesity or signs of diabetes are visible. Hyperinsulinemia was evident in diabetes mice of both strains at 10 days of age and the severity increased progressively with age. These elevated concentrations of plasma insulin were associated with mild hypoglycemia. No significant differences were observed with respect to the degrees of hyperinsulinemia or hypoglycemia between diabetes mice of the two strains. The mild hypoglycemia observed in diabetes mice in the presence of a pronounced hyperinsulinemia suggests that insulin resistance occurs as early as age 10 days and may itself be a factor in causing hyperinsulinemia. The sequence of early events occurring in diabetes mice appears to be hyperinsulinemia leading to mild hypoglycemia, followed by compensatory hyperphagia which in turn results in enhanced insulin secretion and obesity.