Tumor Effects on Gluconeogenesis in the Isolated Perfused Rat Liver

Abstract

Alterations in metabolism in the tumor-bearing host can be explained by: 1) alterations of metabolic processes in the tumor itself, and/or 2) tumor effects on host metabolism. Tumor effects on host liver metabolism were studied using an isolated perfused rat liver preparation. The livers of fasted female Lewis Wistar rats with and without transplanted subcutaneous mammary tumors were perfused for 1 hr with medium containing 5 mM glucose and physiological levels of amino acids. The rate of gluconeogenesis, as measured by conversion of ¹⁴C-lactate to ¹⁴C-glucose, showed a significant increase in the rate of glucose production from lactate in tumor-bearing rats (2.40 vs 2.00 μmol/min/100 gm). Hepatic glycogen and ¹⁴C-glycogen content were not significantly different between the two groups. In order to evaluate whether this tumor model exhibits characteristic changes in metabolism previously reported in other animal tumor models, serum lactate, triglyceride, glucose, and blood urea nitrogen were measured in non-perfused animals. The serum concentration of lactate and triglycerides were significantly higher in tumor-bearing rats (0.9 mM vs 2.7 mM lactate; 244 mg % vs 365.5 mg % triglycerides). Serum glucose and blood urea nitrogen were not significantly different in the two groups. An effect of tumor on host energy metabolism and serum metabolite levels is demonstrated. A method for the study of host-tumor metabolic interactions is described.