Calcium-dependent regulation of glucose homeostasis in the liver

A major role of the liver is to integrate multiple signals to maintain normal blood glucose levels. The balance between glucose storage and mobilization is primarily regulated by the counteracting effects of insulin and glucagon. However, numerous signals converge in the liver to ensure energy demand matches the physiological status of the organism. Many circulating hormones regulate glycogenolysis, gluconeogenesis and mitochondrial metabolism by calcium-dependent signaling mechanisms that manifest as cytosolic Ca2+ oscillations. Stimulus-strength is encoded in the Ca2+ oscillation frequency, and also by the range of intercellular Ca2+ wave propagation in the intact liver. In this article, we describe how Ca2+ oscillations and waves can regulate glucose output and oxidative metabolism in the intact liver; how multiple stimuli are decoded though Ca2+ signaling at the organ level, and the implications of Ca2+ signal dysregulation in diseases such as metabolic syndrome and non-alcoholic fatty liver disease.