Glucagon is a 29-amino-acid peptide hormone liberated in the alpha cells of the islets of Langerhans. Glucagon-producing alpha cells represent one of the earliest populations of detectable islet cells in the developing endocrine pancreas. Glucagon is generally viewed as a hormone that opposes the action of insulin in peripheral tissues, predominantly the liver, where the insulin:glucagon ratio determines the intricate control of gluconeogenesis and glycogenolysis. The action of glucagon in the liver is complex and involves coordinate regulation of transcription factors and signal transduction networks which converge on regulation of amino acid, lipid and carbohydrate metabolism.