Development of the obese-hyperglycaemic syndrome in mice

Abstract

Mice with the recessively inherited, obese-hyperglycaemic syndrome were studied at different stages of their development. Homozygous carriers of the syndrome already exhibited an excessive accumulation of fat resulting in overweight at an age of 26 days. A few days later the concentration of serum immunoreactive insulin was raised and then continuously increased until about 6 months of age. Subsequently there was a gradual decline to the levels observed in the lean litter mates. Serum glucose values above those of the lean controls were first observed at about 1 month of age. There was a subsequent increase of the blood sugar values until the mice were 3 months old, when the mean value was above 300 mg per 100 ml. The level then decreased until in 7 months old obese mice it did not differ from that in the lean litter mates. The concentration of serum free fatty acids of the obese mice was not significantly different from that of their lean litter mates; a decrease with age being observed for both types. In the old obese mice there was a fall also in the body weight to approximately normal levels. - Administration of insulin to the genetically future-obese mice displayed a higher insulin tolerance as reflected in a slower decrease of the blood sugar level at an age of 27 days. The ability of these mice to resist insulin-induced convulsions was tried as a method for an early identification of individual future-obese mice. It was, however, not possible to classify the mice completely into two genetically different groups at 23-25 days of age, although this test turned out to be fairly reliable. Glucose tolerance tests at the same early age were also found to be less useful. Only in 4 months old, obese-hyperglycaemic mice did an intraperitoneal glucose load result in a slower return of the blood sugar level to the pre-injection value. - The present findings indicate a triphasic development of the obese-hyperglycaemic syndrome. After an initial asymptomatic period lasting for the first 23-26 days of life, the various manifestations of the syndrome appear in the course of a few days. The subsequent period is characterized by increasing serum glucose and insulin concentrations and coincides approximately with the time of rapid gain in body weight. After the body growth ceases the abnormalities associated with the syndrome gradually disappear. The pattern of development of the syndrome is compatible with the view that diabetogenic factors are active during a limited period early in the life of the homozygous mice. © 1968 Springer-Verlag.