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 one week the pedicle of the auto graft was clamped for thirty to sixty minutes. In seven 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 seven fasting dogs the blood glucose level was rising in the four- to tenminute interval after clamping. In three such dogs (one under local and two 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 one third at one to thirteen minutes 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 (unclamping) 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 fifteen hours, 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 to prevent glucose accumulation in the partially depancreatized dog.