The reversal of increased gluconeogenesis in the tumor-bearing rat by tumor removal and food intake.
The accelerated mobilization of peripheral protein and subsequent increased gluconeogenesis are regarded as mechanisms of cancer cachexia. To determine the relation of gluconeogenesis to different degrees of tumor burden and subsequent tumor removal in the fed and fasted states, we examined the activity and mRNA levels of the key regulatory enzyme for gluconeogenesis: phosphoenolpyruvate carboxykinase (PEPck) in the liver of Fischer rats with a transplanted methylcholanthrene-induced sarcoma. PEPck activity in liver cytosol, after a 24-hour fast, was significantly higher in the tumor-bearing rats than in their pair-fed controls. The increase in enzyme activity was clearly evident at 8% tumor burden and correlated positively with the degree of tumor burden (r = 0.85, p less than 0.01). Removal of the tumor produced a complete reversal of PEPck activity 10 days after excision. Regular feeding also abolished this increased enzyme activity. A similar trend was seen in the mitochondria. PEPck mRNA levels of rats with greater than 11% tumor burden in the fed state were decreased more than those of controls. PEPck mRNA levels were equally elevated in tumor bearers and controls in the 24-hour-fasted state. These results suggest that tumor-bearing simulates the fasted state associated with hypoglycemia, which in turn triggers induction of the gluconeogenic enzyme, PEPck.
Memorial Sloan-Kettering Cancer Center, Surgical Metabolism Laboratory, New York, NY 10021.
Y
Y
Noguchi
N A
NA
Vydelingum
M F
MF
Brennan
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D004435:Eating; D005215:Fasting; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012513:Sarcoma, Experimental / Q000378:metabolism* / Q000473:pathology / Q000601:surgery
D012333:RNA, Messenger; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose