Progressive Decreased Glucose-tolerance and Glycogen-storage Following Acetoacetate Injection;Prevention by Insulin and Amellin

Abstract

Summary

1. The repeated daily injection of sodium acetoacetate in progressively increasing doses (beginning at 50 mg/kg body weight) caused a progressive hyperglycemia in rabbits after an initial hypoglycemic stage. 2. The glucose tolerance of these animals was decreased after 30 days of injection and the tolerance curve taken at 30, 50, 70, 90, 110 and 130 days became progressively more diabetic. 3. The shape of the tolerance curves changed considerably on prolonged treatment with acetoacetate and in most cases the blood sugar levels at 3 1/2 hours were far greater than the pre-injection level. 4. The glycogen content of liver and muscle is gradually depleted, so that after 130 days of injection it was decreased 64.9% and 73.4% respectively. 5. When Amellin was injected daily for 40 days in doses of 10-12 mg/kg into these hyperglycemia animals it reduced the blood sugar to 105 mg/100 cc (normal value). Insulin, although it relieved the fasting hyperglycemia initially, had little effect on the fasting hyperglycemia in later stages. Increasing the insulin dose leads to death. 6. The glucose tolerance of the animals treated with sodium acetoacetate became absolutely normal after Amellin had administered for 40 days, whereas the tolerance of similar animals treated with insulin was not normal at 40 days.