Insulin is a peptide hormone that plays a critical role in human metabolism. It is synthesized and secreted by beta cells of Islets of Langerhans in the pancreas. It is the first peptide hormone to be discovered (by Frederick Banting and Charles Herbert Best, 1921). It is the first protein to be sequenced in 1951 by Frederick Sanger. Dorothy Hodgkin has determined the crystal structure of insulin in 1969. Nevertheless, it is the first hormone to be synthesized by recombinant DNA technology.
Human insulin is made up two polypeptide chains of 51 amino acids (A-chain- 21 amino acids and B-chain, 30 amino acids) with a molecular mass of 5808 Daltons. Insulin is an anabolic hormone that plays a crucial role in the metabolism of carbohydrates and fats by converting the free glucose available in the blood into glycogen that can be stored in the muscles.
Insulin is synthesized as a single polypeptide called ‘preproinsulin’ along with a 24 residue signal peptide in the pancreatic beta cells. The signal peptide guides preproinsulin to endoplasmic reticulum (ER), where the signal peptide gets separated, resulting in ‘proinsulin’ formation. In the ER, the proinsulin is further processed and folded with the formation of three disulphide bonds and gets transported to golgi complex. In golgi, the folded proinsulin is converted to ‘active insulin’ by cellular endopeptidases, namely prohormone convertases 1 & 2 and exoprotease carboxypeptidase E. These endonucleases cleave at two positions in the proinsulin, resulting in the separation of a fragment called C-peptide. The active and mature insulin now consists of two chains: A-chain (21 amino acids) and B-chain (30 amino acids), both liked to each other by two disulphide bonds.