Insulin: Biosynthesis, Chemistry, and Preparation

The pancreatic β-cell's endoplasmic reticulum synthesizes preproinsulin comprising a signal peptide, B and A chains, and a C-peptide. The cleavage of signal peptide and the formation of disulfide bond yield proinsulin, which is then transported to the Golgi apparatus.

Afterward, prohormone convertases snip proinsulin, separating C-peptide and insulin containing disulfide-linked A and B chains, stored together in granules.

β-cell damage or functional impairment suppresses insulin production, causing diabetes featuring hyperglycemia.

Diabetes therapy mainly involves recombinant human insulin as regular or neutral protamine hagedorn formulations.

Additionally, modifying amino acid sequences or insulin structure creates rapid-acting or long-acting analogs.

For example, insulin lispro, formed by reversing the 28th and 29th amino acids in the B chain, allows rapid absorption by monomer formation.

Insulin glargine replaces Asn at the 21 position with Gly and extends the B chain by adding two Arg. Once injected, it precipitates at pH 7.4, slowing absorption and prolonging action.