Effects of Sudden Deprivation and Restoration of Insulin Secretion on Glucose Metabolism in Dogs

Abstract

Fourteen subtotally depancreatized aglycosuric dogs had the remaining pedunculated uncinate process enclosed in plastic casing and grafted subcutaneously. After 1 week the pedicle of the autograft was clamped for 30 to 60 min. In 7 dogs given intravenous glucose at the time of clamping, diabetes-like changes in glucose tolerance occurred which increased in magnitude with increasing duration of deprivation of exogenous insulin. In 7 fasting dogs the blood glucose level was rising in the 4-to 10-min. interval after clamping. In 3 such dogs (1 under local and 2 under Nembutal anesthesia) the method of successive measured injections of tracer (C-14-glucose U.L.) showed that the rate of glucose appearance had doubled and the rate of its disappearance was decreased to 1/3 at one to 13 min. after clamping, resulting in high rates of accumulation of body glucose. The initial increase in the rate of glucose production appears to result from glycogenolysis. Restoration of blood flow through the autograft (un-clamping) caused a prompt decrease in rate of appearance of unlabeled glucose and increase in its rate of disappearance, resulting in restoration of these rates to their preclamping values within 15 hr., and to a restored tolerance for intravenous glucose. The rapidity of these rate changes at clamping and unclamping demonstrates the importance of the continuous secretion of native insulin in prevent glucose accumulation in the partially depancreatized dog.