Dietary Pi deprivation in rats affects liver cAMP, glycogen, key steps of gluconeogenesis and glucose production

Abstract

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.