Up-regulation of liver glucose-6-phosphatase in rats fed with a P-i-deficient diet

Because P-i deprivation markedly affects the Na/P-i co-transporter in kidne y and has been related to insulin resistance and glucose intolerance,the ef fect of a P-i-deficient diet on the liver microsomal glucose-6-phosphatase (G6Pase) system was investigated. Rats were fed with a Control diet (+ P-i) or a diet deficient in phosphate (- P-i) for 2 days and killed on the morn ing of the third day, after an overnight fast: (fasted) or not (fed), Kinet ic parameters of P-i transport (t(1/2) and equilibration) into liver micros omes were not changed by the different nutritional conditions, In contrast, it was Found that G6Pase activity was significantly increased in the (-P-i ) groups. This was due to an increase in the V-max of the enzyme, without. Change in the K-m for G6P. There was no correlation between liver microsoma l glycogen content and G6Pase activity, but both protein abundance and mRNA of liver 36 kDa catalytic subunit of G6Pase (p36) were increased. The mRNA of the putative G6P translocase protein (p46) was changed in parallel with that of the catalytic subunit, but the p46 immunoreactive protein was unch anged. These findings indicate that dietary P-i deficiency causes increased G6Pase activity by upregulation of the expression of the 36 kDa-catalytic- subunit gene.