Give an account of the physiological role and functions of glucagon.

Outline:

·        Regulation of secretion

·        Direction of substrate flow depends on Insulin:glucagon ratio

·        Role in preventing hypoglycaemia

Essay:

   Glucagon is a single, straight-chain peptide hormone of 29 amino acids and molecular weight of 3500. The most important principle governing glucagon secretion is the maintenance of normal blood glucose level in the face of increased tissue glucose demand. Glucagon is secreted in response to glucose deficiency and acts to increase circulating glucose levels. Glucagon secretion is also stimulated by a protein meal and, most effectively, by amino acids such as arginine and alanine.

            Glucagon promotes mobilization rather than storage of fuels, especially glucose. Glucagon binds to a hepatic plasma membrane glycoprotein receptor; the resultant signal is transduced via a stimulatory G protein, adenyly cyclase, and cAMP as second messenger. The dominant effect of glucagon is on the liver. Glucagon stimulates glycogenolysis, gluconeogenesis and increases hepatic extraction of amino acids.

            The direction of substrate fluxes is very sensitive to the relative availability of insulin and glucagon. The usual molar ratio of insulin to glucagon in plasma is about 2.0. Under circumstances that requires mobilization and increased use of endogenous substrates, the insulin:glucagon ratio drops to 0.5 or less. This decreased ratio is seen in fasting and in prolonged exercise, and is caused by both decreased insulin secretion and increased glucagon secretion. A low insulin:glucagon ratio facilitates increased glycogenolysis, amino acid mobilization, and gluconeogenesis to maintain glucose supply to the nervous system. Lipolysis is also enhanced, which increases free fatty acid flow to muscle and liver for oxidation. During exercise, the low insulin:glucagon ratio still permits muscle glucose uptake, which is stimulated by an exercise-specific mechanism that is independent of insulin.

            Conversely, under circumstances in which substrate storage is advantageous, such as after a pure carbohydrate load or a mixed meal, the insulin:glucagon ratio rises to 10 or more, mainly because of increased insulin secretion. The high ratio enhances glucose uptake, oxidation, and conversion to liver and muscle glycogen, while it suppresses unneeded proteolysis and lipolysis. However, only a small and insignificant change in the insulin:glucagon ratio occurs after a subject ingests a pure protein meal. In this situation, insulin secretion increases, preventing unneeded proteolysis and facilitating muscle uptake of some amino acids and their incorporation into proteins. At the same time, glucagon secretion also increases. This increase in glucagon prevents the decrease in hepatic glucose output and hypoglycaemia that would ensue if the extra insulin action were completely unopposed.