John S. Cowan

Glucoregulatory responses in normal and diabetic dogs recorded by a new tracer method

Abstract A modification of the primed tracer infusion technique has been developed that permits the calculation of the rates of glucose production (Ra) and utilization (Rd) as continuous functions of time. A correction for the recycling of label into newly released glucose is also introduced. In normal dogs insulin (0.06 IU/kg i.v.) appreciably decreased Ra and increased Rd within 4 min during which time the glucose concentration in the plasma fell by only about 2–4 mg 100 ml . In normal dogs the intravenous injection of 0.18–0.29 g/kg glucose decreased Ra and abruptly increased Rd. The changes in Ra and Rd with respect to time followed oscillations typical of underdamped harmonic motion. In diabetic dogs the decrease of Ra was less or absent and the restoration of the basal plasma glucose level was largely due to an increase of Rd. These experiments allowed the estimation of the “pool fraction” which averaged 65 per cent of the total glucose pool in normal and 86 per cent in diabetic dogs.

Effects of sudden deprivation and restoration of insulin secretion on glucose metabolism in dogs.

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.

Absolute Rates of Glucose Production, Accumulation, and Utilization in the Dog at Pancreatectomy and Thereafter

1. The method of successive measured injections of tracer has been used to determine absolute rates of glucose appearance (production), accumulation, disappearance, excretion and utilization in six fasting bitches at times before and after total pancreatectomy. 2. The rate of glucose utilization underwent a great reduction within minutes following pancreatectomy. 3. In contrast, the rate of glucose production did not change greatly at this time. 4. As a consequence, there was a rapid accumulation of glucose in the dog when measured in terms of the amount which intermixed with the injected tracer, and as seen less directly by a rise in the concentration of glucose in the blood plasma. 5. The increase in blood glucose level following pancreatectomy was accompanied by a restoration in the average rate of glucose utilization to about two thirds of its value before pancreatectomy, and by glycosuria. 6. Both the rate of production and that of utilization increased moderately during the first one or two days following total pancreatectomy. Thereafter they decreased progressively and ketonuria became severe. 7. No effect of general anesthesia (Nembutal) was noted on the above patterns of change in glucose rates.

Nutritional Conditions Affecting the Rate of Glucose Production in Fed and Fasting Female Dogs

Abstract The endogenous rate of glucose production in female dogs decreased progressively during fasting in each of 11 experiments. Rates were determined by a validated tracer method. After preconditioning on diets high in carbohydrate, protein or fat, approximately the same equifinal rate of endogenous glucose production was approached rapidly, less rapidly and slowly, respectively, in nondiabetic female dogs during the 3 days following the last meal. The rate was significantly higher in 4 female dogs with Sandmeyer-diabetes and in one nondiabetic subject 35 days prepartum, in each case after 3 days of fasting. All animals were aglycosuric and near dynamic steady states for glucose.