The role of intracellular Ca2+ in the regulation of gluconeogenesis

A hypothesis for the hormonal regulation of gluconeogenesis, in which increases in cytosolic free-Ca2+ levels ([Ca2+]i) play a major role, is presented. This hypothesis is based on the observation that gluconeogenic hormones evoke a common pattern of Ca2+ redistribution, resulting in increases in [Ca2+]i. Current concepts of hormonally evoked Ca2+ fluxes are presented and discussed. It is suggested that the increase in [Ca2+]i is functionally linked to stimulation of gluconeogenesis. The stimulation of gluconeogenesis is accomplished in two ways: (1) by increasing the activities of the Krebs cycle and the electron-transfer chain, thereby supplying adenosine triphosphates (ATP) and reducing equivalents to the process; and (2) by stimulating the activities of key gluconeogenic enzymes, such as pyruvate carboxylase. The hypothesis presents a conceptual framework that ties together two interrelated manifestations of hormone action: signal transduction and metabolism.