Proinsulin (PI)

Proinsulin is synthesized in the pancreatic beta cells as a 9390 mw polypeptide of 86 amino acids. Proinsulin is subsequently cleaved enzymatically, releasing insulin into the circulation along with a residual 3000 mw fragment called C-peptide, so-named because it connects the A and B chains of insulin within the proinsulin molecule.

Proinsulin, which has relatively low biological activity (approximately 10% of insulin potency), is the major storage form of insulin. Normally, only small amounts (~3% of the amount of insulin, on a molar basis) of proinsulin enter the circulation. Because the hepatic clearance of proinsulin is only 25% of insulin clearance, the half-life of proinsulin is two- to threefold longer and concentrations in the fasting state are approximately 10% to 15% of insulin concentrations.