Pancreatic β-cells couple the oxidation of glucose to the secretion of insulin. Apart from the
canonical K ATP-dependent glucose-stimulated insulin secretion (GSIS), there are important
K ATP-independent mechanisms involving both anaplerosis and mitochondrial GTP
(mtGTP). How mtGTP that is trapped within the mitochondrial matrix regulates the cytosolic
calcium increases that drive GSIS remains a mystery. Here we have investigated whether
the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK-M) is the GTPase …