Parenteral level of glucose intake on glucose homeostasis, tumor growth, gluconeogenesis, and body composition in normal and tumor-bearing rats.

To determine the effects of different levels of glucose intake on glucose homeostasis, gluconeogenesis, body composition, and tumor growth, we gave 8 days of total parenteral feeding of a defined liquid formula diet to groups of Buffalo rats, with and without a transplantable Morris 7777 hepatoma. The level of glucose intake was held at levels which ranged from 0 to 9.5 g/100 body weight per day while the levels of all other nutrients were held constant. Measurements were made on tumor growth rate, terminal blood plasma glucose and whole blood lactate levels, gluconeogenesis, body and organ weight, muscle nitrogen content, liver glycogen, and urine analysis. Tumor-bearing rats (TB) at low glucose intake but not non-tumor-bearing rats (NTB) were found to be dependent on gluconeogenesis for maintenance of blood glucose homeostasis (normoglycemia). Body weight was dependent on glucose intake level in both TB and NTB rats with glucose intake rates of 5.7 g/100 g/day being the point between weight loss or gain. However, under these feeding conditions, tumor growth rate was not dependent on the glucose intake rate. The weight of epididymal fat pad and the size of fat cells were positively correlated with glucose intake rate in both TB and NTB rats, but the fat pad weight in TB rats showed a greater dependence on the rate of glucose intake than it did in the NTB rats. Glucose intake of 3.8 g/100 g/day or less leads to significant loss of muscle mass and loss of muscle nitrogen (protein) in TB but not in NTB rats. Some liver glycogen was detected in all groups of rats except those TB rats with zero glucose intake. TB rats with high glucose intake (5.7 to 9.5 g/100 g/day) had higher blood lactate and lower urine pH than did NTB rats. Thus, TB rats at low glucose intake (3.8 g/100 g/day or less), as opposed to NTB rats, demonstrated a significant dependence on gluconeogenesis for glucose homeostasis, mobilized more of their liver glycogen, and catabolized more of their muscle proteins to supply the increased energy needs of the growing tumor and to maintain normoglycemia.