Regulation of renal gluconeogenesis by calcium ions, hormones and adenosine 3′:5′-cyclic monophosphate

1. The effect of Ca2+, glucagon, adrenaline and adenosine 3′:5′-cyclic monophosphate on gluconeogenesis by rat kidney-cortex slices was studied. 2. Glucose formation from a range of substrates, with the exception of glycerol, was increased by an increase in extracellular Ca2+ concentration. 3. Hormones and adenosine 3′:5′-cyclic monophosphate, at low Ca2+ concentrations, stimulated glucose production from several substrates, but not from glycerol, fructose, malate or fumarate. 4. Hormonal stimulation was not detected in the absence of Ca2+ or at 2.5mm-Ca2+. 5. Ca2+, hormones and adenosine 3′:5′-cyclic monophosphate had no effect on phosphoenolpyruvate carboxylase activity. 6. It is proposed that Ca2+ and adenosine 3′:5′-cyclic monophosphate-mediated hormone action activate the same rate-limiting step in gluconeogenesis: this step is tentatively identified as the rate of transfer of substrates across the mitochondrial membrane.