Insulin

Physiology

Human insulin is a polypeptide of 51 amino acids and is formed by the removal of a connecting or ‘C’ peptide (34 amino acids) from pro-insulin. It has A and B chains, which are joined by two disulphide bridges. A third disulphide bridge connects two regions of the A chain.

Glucose forms the most potent stimulus for insulin release. It enters the β-cells of the islets of Langerhans in the pancreas, resulting in an increase in ATP, which closes K+ channels. This causes depolarization and Ca2+ influx through voltage-sensitive Ca2+ channels, which triggers insulin release. By way of negative feedback the K+ channels are re-opened. In health there is a continuous basal insulin release, which is supplemented by bursts when plasma glucose levels rise. Following its release it is carried in the portal circulation to the liver (its main target organ) where about one-half is extracted and broken down, as glucose is converted to glycogen.

Insulin binds to the α subunit of the insulin receptor, which consist of two α and two β subunits that span the cell membrane. Once bound, the whole complex is internalized. The mechanism by which this complex produces its effects is unclear but the tyrosine kinase activity of the β subunit appears important.

Insulin affects carbohydrate, fat and protein metabolism. It promotes hepatic (and extrahepatic) uptake of glucose and subsequently facilitates the actions of enzymes required to convert glucose into glycogen. Glycogenolysis is inhibited.