POST-WEANING DEVELOPMENT OF DIABETES IN OB-OB MICE

In association with moderate diabetes, fully mature obese mice ( C57BL 6J ob ob) display several disturbances of metabolism, behavior, and growth. As yet, no precise developmental relationships have been established between the major abnormalities of these mice, although obesity, hypometabolism, and reduced activity have been reported as early as 7 days of age and appear to precede the development of diabetes. In the present studies, examination of glucose regulation revealed that preweanling obese mice, which are already characterized by many metabolic and growth deficits, had significantly lower fasting glucose levels when compared with lean controls, and displayed subnormal glycemia in response to glucose or control stimulation. In contrast, 28-day-old mutant mice had mildly elevated fasting glucose levels and maintained severe hyperglycemia after either glucose or distilled water administration. In response to exogenous insulin (1 U/kg), obese mice at each age displayed significant reductions of serum glucose, but appeared to be mildly insulin-insensitive when their glucose responses were compared with those of lean mice. The present results suggest that several factors are likely to be responsible for the rapid postweaning development of diabetes in ob ob mice, including insulin resistance, dietary changes, and, possibly, an increased capacity for diabetogenic hormone production; however, the appearance of diabetes substantially later than several other metabolic disturbances indicates that abnormal glycoregulation is a relatively indirect consequence of the ob ob mutation. © 1979.