CONICET | Buscador de Institutos y Recursos Humanos

Blood glucose, the natural source of energy substrate for cells in intact animals, must be maintained within a tight range to cope with the cell demand. Since glycaemia fluctuates according to the fasting and feeding states, the liver plays a key role in glucose homeostasis either increasing or decreasing glucose output and uptake. In this context, liver glucokinase (GCK) becomes a key player, and a complex net of mechanisms modulate its activity in a coordinated manner: in the postprandial period, the simultaneous rise in blood glucose and insulin increases GCK activity by combining enhanced gene expression, changes in cellular location, and interaction with regulatory proteins. Conversely, in the fasting state, the low blood glucose and insulin concentration, together with a rise in glucagon concentration, shuts down GCK activity. This review summarizes the current knowledge about the mechanisms involved in the regulation of hepatic GCK activity.