We previously reported [Xie, Li, Méchin and van de Werve (1999) Biochem. J. 343, 393-396] that dietary
phosphate deprivation for 2 days up-regulated both the catalytic subunit and the putative
glucose-6-phosphate translocase of the rat liver microsomal
glucose-6-phosphatase system, suggesting that increased hepatic
glucose production might be responsible for the frequent clinical association of hypophosphataemia and
glucose intolerance. We now show that liver cAMP was increased in rats fed with a diet deficient in P(i) compared with rats fed with a control diet. Accordingly, in the P(i)-deficient group
pyruvate kinase was inactivated, the concentration of
phosphoenolpyruvate was increased and
fructose 2, 6-bisphosphate concentration was decreased.
Phosphoenolpyruvate carboxykinase activity was marginally increased and
glucokinase activity was unchanged by P(i) deprivation. The
liver glycogen concentration decreased in the P(i)-deficient group. In the fed state, plasma
glucose concentration was increased and plasma P(i) and
insulin concentrations were substantially decreased in the P(i)-deficient group. All of these changes, except decreased plasma P(i), were cancelled in the overnight fasted P(i)-deficient group. In the fasted P(i)-deficient group, immediately after a
glucose bolus, the plasma
glucose level was elevated and the inhibition of endogenous
glucose production was decreased. However, this mild
glucose intolerance was not sufficient to affect the rate of fall of the
glucose level after the
glucose bolus. Taken together, these changes are compatible with a stimulation of liver gluconeogenesis and glycogenolysis by the P(i)-deficient diet and further indicate that the liver might contribute to impaired
glucose homeostasis in P(i)-deficient states.