preproinsulin

Preproinsulin is the initial translation product of the insulin gene (INS) in pancreatic beta cells. It contains an N-terminal signal peptide that directs the nascent peptide to the endoplasmic reticulum, where the signal peptide is cleaved to yield proinsulin.

In the secretory pathway, proinsulin folds and forms disulfide bonds, then is trafficked to the Golgi apparatus and secretory granules. In these granules, endopeptidases known as prohormone convertases (PC1/3 and PC2) cleave proinsulin at dibasic sites to release insulin and C-peptide; carboxypeptidase E trims remaining residues to generate mature insulin.

Mature insulin consists of two polypeptide chains, A and B, linked by two interchain disulfide bonds, with an additional intrachain disulfide bond within the A chain. The C-peptide is removed during processing but is secreted in equimolar amounts with insulin, making it a useful biomarker of endogenous insulin production.

The INS gene is expressed in pancreatic beta cells and encodes a preprohormone that governs insulin biosynthesis and secretion in response to glucose. Proper processing of preproinsulin is essential for normal insulin function and glucose homeostasis; defects in this pathway can impact insulin availability and metabolic regulation.