The Glucagon Receptor mediates the effects of glucagon in controlling glucose metabolism by initiating a cascade of events that regulate the amount of glucose released from the liver into the bloodstream. Glucagon generally functions as a counterregulatory hormone, opposing the actions of insulin, in maintaining the levels of blood glucose, particularly in patients with hypoglycemia. In patients with diabetes, excess glucagon secretion plays a primary role in the metabolic perturbations associated with diabetes, such as hyperglycemia. Glucagon knockout mice exhibit reduced glood glucose levels, improved glucose tolerance, elevated blood glucagon levels, and normal insulin levels. Despite a total absence of glucagon receptors, these animals maintained near-normal glycemia and normal lipidemia, in the presence of circulating glucagon concentrations that were elevated by two orders of magnitude. A missense mutation (Gly40Ser) in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus. The glucagon receptor has been reported to be expressed in liver and adipose, but not in adrenal medulla. ESTs have been isolated from liver/spleen and kidney libraries.