INSULIN-TREATMENT INHIBITS GLUCOSE AND GLUTAMINE-METABOLISM - IN TUMOR-CELLS FROM WALKER-256 TUMOR-BEARING RATS

Cancer cachexia is a syndrome seen in Walker 256 tumor-bearing animals . The administration of insulin to a Walker 256 tumor-bearing rats ame lliorates cancer cachexia and decreases tumor growth. This study exami ned the effect of insulin treatment (4U/100 g b.w.) during 10 days on glucose and glutamine metabolism in the tumor cells from Walker 256 tu mor-bearing rats. Also activity of hexokinase, glucose-6-phosphate deh ydrogenase, citrate synthase and the amount of GLUT1 and GLUT4 was det ermined. The insulin treatment reduced 80% lactate production and 90% the decarboxylation of [U-C-14]-glucose, increased the conversion of g lutamine to glutamate (32%) and aspartate (54%) and diminished in 80% the decarboxylation of [U-C-14]-glutamine in incubated tumor cells. Th e amount of GLUT1 in the Walker 256 tissue was not significantly chang ed by insulin treatment. The activity of hexokinase (E.C. 2.7.1.1) and phosphate-dependent glutaminase (E.C. 3.5.1.2.) was reduced in 9% and 45%, respectively. Citrate synthase (E.C. 4.1.3.7.) hummed 74% with n o change in the G-6-PDh (E.C. 1.1.1.49) activity due to insulin treatm ent. Our results suggest that insulin treatment under this condition m ight reduce the utilization of glucose and glutamine by tumor tissue, leading to cell death.