The role of calcium in renal gluconeogenesis: studies using ionophore A23187

The divalent cation ionophore A23187 was found to increase glucose production from alpha-ketoglutarate, glutamine, succinate, and lactate but not from glycerol in isolated rat renal cortical tubules at external Ca++ concentrations of 0.1 mM. At an external Ca++ concentration of 1.0 mM or in the absence of external Ca++, the ionophore did not increase glucose production from alpha-ketoglutarate. Ionophore A 23187 did not increase cyclic AMP levels in renal cortical tubules or slices. The increase in glucose production produced by ionophore A23187 was completely prevented by pre-incubation of the tubules with 10(-5) M pentobarbital, a known inhibitor of calcium transport in biological systems. The experiments suggest that ionophore A23187 increases gluconeogenesis from a variety of substrates by altering the levels of cytosolic calcium without affecting the concentrations of cyclic AMP.