PHYSIOLOGY OF INSULIN

What is insulin?

Insulin is a hormone which is secreted by the pancreatic beta cells. It is a protein. This hormone is essential for the metabolism of carbohydrates, protein and fat.

Biosynthesize

Insulin is produced in the beta cells of the pancreatic islets. It is initially synthesized as a single-chain 86-amino-acid precursor polypeptide, preproinsulin. Subsequent proteolytic processing removes the aminoterminal signal peptide, giving rise to proinsulin. Proinsulin is structurally related to insulin-like growth factors I and II, which bind weakly to the insulin receptor. Cleavage of an internal 31-residue fragment from proinsulin generates the C peptide and the A (21 amino acids) and B (30 amino acids) chains of insulin, which are connected by disulfide bonds.

The mature insulin molecule and C peptide are stored together and cosecreted from secretory granules in the beta cells. Because the C peptide is less susceptible than insulin to hepatic degradation, it is a useful marker of insulin secretion

Secretion

Glucose enters to the beta cells via GLUT 2 receptors

Metabolized by the Glucokinase

Produce ATP

ATP inhibits potassium channel

Depolarization of the cell membrane

Opening of voltage dependant calcium channel

calcium influx


Insulin secretion





Action

Insulin acts on almost all the tissues but liver, muscles and adipose tissues are the main sites. Overall effect is to conserve fuel by facilitating the uptake and storage of glucose , amino acids and fatty acids following a meal.

Insulin binding to its receptor stimulates intrinsic tyrosine kinase activity, leading to receptor autophosphorylation and the recruitment of intracellular signaling molecules, such as insulin receptor substrates (IRS). These and other adaptor proteins initiate a complex cascade of phosphorylation and dephosphorylation reactions, resulting in
the widespread metabolic and mitogenic effects of insulin.


Structure

Insulin consists of two amino acids; A chain (21 amino acids): B chain (30 amino acids).
These two amino acids chains are combined with two sulphide bonds.