Glucagon

Glucagon

Glucagon is an important hormone that is involved in the metabolism of carbohydrates. It is produced by the pancreas, which is released when the level of glucose in the blood is low. This will cause the liver to convert the stored glycogen into glucose and released into the bloodstream. Glucagon is often described as having the opposite effect of insulin, which instructs the cells of the body to take in glucose from the blood. Glucagon also stimulates the release of insulin, so that newly available glucose in the bloodstream can be taken up and used by insulin-depende.

Production of Glucagon

The hormone is synthesized and secreted from alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. In rodents, the alpha cells are located in the outer rim of the islet. Human islet structure is much less segregated, and alpha cells are distributed throughout the islet.

Functions

Glucagon helps maintain the level of glucose in the blood by binding to glucagon receptors on hepatocytes, causing the liver to release glucose stored in the form of glycogen through a process known as glycogenolysis. Glucagon stimulates breakdown of glycogen stored in the liver. blood glucose levels are high, large amounts of glucose are taken up by the liver. Under the influence of insulin, much of this glucose is stored in the form of glycogen. Later, when blood glucose levels begin to fall, glucagon is secreted and acts on hepatocytes to activate the enzymes that depolymerize glycogen and release glucose. As these stores become depleted, glucagon then encourages the liver to synthesize additional glucose by gluconeogenesis. Glucagon activates hepatic gluconeogenesis. Gluconeogenesis is the pathway by which non-hexose substrates such as amino acids are converted to glucose. As such, it provides another source of glucose for blood. This is especially important in animals like cats and sheep that don't absorb much if any glucose from the intestine - in these species, activation of gluconeogenic enzymes is the chief mechanism by which glucagon does its job. This glucose is released into the bloodstream. Both of these mechanisms lead to glucose release by the liver, preventing the development of hypoglycemia. Glucagon also appears to have a minor effect of enhancing lipolysis of triglyceride in adipose tissue, which could be viewed as an addition means of conserving blood glucose by providing fatty acid fuel to most cells.

Regulatory Mechanism

Increase secretion of glucagon is caused by the following:

· Decreased plasma glucose

· Increased catecholamines- norepinephrine and epinephrine

· Increased plasma amino acids (to protect from hypoglycemia if an all protein meal is consumed)

· Sympathetic nervous system

· Acetylcholine· Cholecystokinin


Decreased secretion of glucagon is caused by the following:

· Somatostatin

· Insulin

· Increased free fatty acids and ketoacids into the blood

Mechanism of Action

Glucagon binds to the glucagon receptor, a G protein-coupled receptor located in the plasma membrane. The conformation change in the receptor activates G proteins, a heterotrimeric protein with α, β, and γ subunits. When the G protein interacts with the receptor, it undergoes a conformational change that results in the GDP molecule, that was bound to the α subunit, to be replaced with a GTP molecule. This substitution results in the α subunit releasing from the β and γ subunit. The alpha subunit specifically activates the next enzyme in the cascade, adenylate cyclase.

Adenylate cyclase manufacture cAMP (cyclical AMP) which activates protein kinase A (cAMP-dependent protein kinase). This enzyme in turn activates phosphorylase kinase, which in turn, phosphorylates glycogen phosphorylase, converting into the active form called phosphorylase A. Phosphorylase A is the enzyme responsible for the release of glucose-1-phosphate from glycogen polymers.

Normal Value: The normal range is 50 to 100 pg/ml.

References:

http://en.wikipedia.org/wiki/Glucagon

http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/pancreas/glucagon.html