Glucose Consumption by Transplanted Tumors in Vivo

Summary

The relationship between availability and utilization of glucose and production of lactate was studied in vivo in Walker carcinoma 256, Hepatoma 5123, and Fibrosarcoma 4956 transplanted in rats. The tumors utilized 0.96, 0.55, and 0.45 gm of glucose/hr/100 gm wet tumor weight, respectively, corresponding to 28%, 23%, and 32% of the amount supplied. About 35% of the glucose consumed was eliminated as lactate regardless of the tumor type. In normoglycemia, the amount of glucose consumed and glycolyzed was directly related to the glucose available which decreased per unit weight as the tumor size increased. During hyperglycemia, produced either by dextrose injections or diabetes, the tumors increased glucose utilization. The increase was maximum during the first few hours; then a “saturation” level was reached. When hyperglycemia was prolonged for several days, carcinomas and hepatomas consistently consumed about ½ more glucose; however, fibrosarcomas reduced their consumption by about 30%. Insulin did not improve glucose consumption of tumors either in normal or diabetic rats. Actually, the overall utilization was reduced because the plasma level of glucose in the host was lowered by insulin. Hypoglycemia or injections of 2-deoxy-d-glucose reduced glucose consumption, and in vivo the tumors were unable to compensate for this decrease by removing more glucose from the blood. The vascular walls of neoplastic vessels maintained a sharp concentration difference between glucose in plasma and in the interstitial fluid, with the fluid surrounding the neoplastic cells containing only a few mg percent of free glucose and practically all of the glucose passing through the vascular walls being rapidly consumed. During hyperglycemia the concentration difference disappeared and the vascular and interstitial compartments had about equal concentrations of glucose. Normo- or hypoglycemia restored the concentration gradient for glucose between the vascular and the interstitial compartment. The time needed to complete the restoration was longer after prolonged hyperglycemia. The regulation of the glucose transfer by the vascular wall of neoplastic vessels is postulated.