Dietary P-i deprivation in rats affects liver cAMP, glycogen, key steps ofgluconeogenesis and glucose production

We previously reported [Xie, Li, Mechin and van de Werve (1999) Biochem. J. 343, 393-396] that dietary phosphate deprivation for 2 days up-regulated b oth the catalytic subunit and the putative glucose-6-phosphate translocase of the rat liver microsomal glucose-6-phosphatase system, suggesting that i ncreased hepatic glucose production might be responsible for the frequent c linical association of hypophosphataemia and glucose intolerance. We now sh ow that liver cAMP was increased in rats fed with a diet deficient in P-i c ompared with rats fed with a control diet. Accordingly, in the P-i-deficien t group pyruvate kinase was inactivated, the concentration of phosphoenolpy ruvate was increased and fructose 2,6-bisphosphate concentration was decrea sed. Phosphoenolpyruvate carboxykinase activity was marginally increased an d glucokinase activity was unchanged by P-i deprivation. The liver glycogen concentration decreased in the P-i-deficient group. In the fed state, plas ma glucose concentration was increased and plasma P-i and insulin concentra tions were substantially decreased in the P-i-deficient group. All of these changes, except decreased plasma P-i, were cancelled in the overnight fast ed P-i-deficient group. In the fasted P-i-deficient group, immediately afte r 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 l evel after the glucose bolus. Taken together, these changes are compatible with a stimulation of liver gluconeogenesis and glycogenolysis by the P-i-d eficient diet and further indicate that the liver might contribute to impai red glucose homeostasis in P-i-deficient states.