Discriminant responses of the catalytic unit and glucose 6-phosphate transporter components of the hepatic glucose-6-phosphatase system in Ehrlich ascites-tumor-bearing mice

The effect of Ehrlich ascites tumor cells, in vivo, on the hepatic glucose- 6-phosphatase (G6Pase) system was examined. The V-max for glucose 6-phospha te hydrolysis by G6Pase was reduced by 40% and a greater than 15-fold decre ase in mRNA encoding the catalytic unit of the G6Pase system was observed 8 days after injection with tumor cells. Blood glucose concentration was dec reased from 169 +/- 17 to 105 +/- 9 mg/dl in tumor-bearing mice. There was no change in the G6P transporter (G6PT) mRNA level. However, there was a si gnificant decrease in G6P accumulation into hepatic microsomal vesicles der ived from tumor-bearing mice. Decreased G6P accumulation was also associate d with a decrease in G6Pase hydrolytic activity in the presence of vanadate , a potent catalytic-unit inhibitor. In addition, G6P accumulation was near ly abolished in microsomes treated with N-bromoacetylethanolamine phosphate , an irreversible inhibitor of the G6PT. These results demonstrate that the catalytic unit and G6PT components of the G6Pase system can be discriminan tly regulated, and that microsomal glucose 6-phosphate uptake is dependent on catalytic unit activity as well as G6PT action. (C) 2001 Academic Press.