ABSTRACT
The effects of high-energy phosphate contents in muscles on glucose tolerance and glucose uptake into tissues were studied in rats and mice. Enhanced glucose tolerance associated with depleted high-energy phosphates and elevated glycogen content in muscles and liver was observed in animals fed creatine analogue beta-guanidinopropionic acid (beta-GPA). Distribution of infused 2-[1-14C]deoxy-D-glucose in tissues especially in the soleus muscle, kidney, and brain was greater in mice fed beta-GPA than controls. The glucose uptake was decreased when the contents of ATP and glycogen were normalized following creatine supplementation. Plasma insulin in animals at rest was lower and its concentration after intraperitoneal glucose infusion tended to be less in animals fed beta-GPA than controls (p > 0.05), although the pattern of insulin response to glucose loading was similar to the control. The daily voluntary activity in beta-GPA fed mice was also less than controls. These results suggest that improved glucose tolerance is not related to elevated insulin concentration and/or decreased glycogen following exercise. Such improvement may be due to an increased mitochondrial energy metabolism caused by depletion of high-energy phosphates.
Subject(s)
Brain/metabolism , Glucose/metabolism , Kidney/metabolism , Muscle, Skeletal/metabolism , Animals , Blood Glucose/metabolism , Brain/drug effects , Deoxyglucose/metabolism , Dose-Response Relationship, Drug , Glucose/administration & dosage , Glucose/pharmacology , Glucose Tolerance Test , Glycogen/metabolism , Guanidines/administration & dosage , Guanidines/pharmacology , Injections, Intraperitoneal , Insulin/blood , Kidney/drug effects , Liver/drug effects , Liver/metabolism , Male , Mice , Muscle, Skeletal/drug effects , Phosphates/metabolism , Physical Conditioning, Animal , Propionates/administration & dosage , Propionates/pharmacology , Random Allocation , Rats , Rats, Wistar , Tissue Distribution/drug effectsABSTRACT
The effect of implantation of Ehrlich ascites tumor (EAT) cells on creatine distribution was investigated. It was also studied how depletion of creatine by feeding creatine-analogue beta-guanidinopropionic acid (beta-GPA) affects the growth of EAT cells in mice. Enhanced mobilization of creatine from host tissues to EAT cells against a greater concentration gradient was observed. The creatine (but not creatinine) level in blood plasma was lowered to 22% of the normal value by beta-GPA feeding alone and assimilation of 14C-creatine into EAT cells was inhibited. The growth of EAT cells was significantly reduced and the duration of survival of mice after implantation of EAT cells was extended when the creatine concentration was decreased. A decrease in daily food consumption and the degree of muscle atrophy after implantation of EAT cells was less in beta-GPA than control groups. In the creatine-depleted mice, the rate of increase in total EAT cell number and the volume of abdominal ascites were approximately half of the control values, and more dead EAT cells were observed. These results suggest that supplementation of beta-GPA inhibits creatine transfer to EAT cells and reduces the growth of cancer cells.
