proinsulina

Proinsulin is the single-chain polypeptide that serves as the precursor to insulin in humans and many other vertebrates. It is produced by pancreatic beta cells in the islets of Langerhans and is encoded by the INS gene. After synthesis in the rough endoplasmic reticulum, proinsulin folds, forms disulfide bonds, and is transported to the Golgi apparatus where it is packaged into secretory granules.

Proinsulin comprises the B chain, C-peptide, and A chain connected in that order (B-C-A). In these secretory granules, two endopeptidases, prohormone convertases PC1/3 and PC2, cleave at dibasic residues to generate insulin and the C-peptide; carboxypeptidase E further processes the products to yield mature insulin consisting of A and B chains linked by disulfide bonds and free C-peptide. Insulin and C-peptide are co-secreted in equimolar amounts in response to glucose.

In the bloodstream, proinsulin represents a small fraction of circulating insulin-like immunoreactivity in healthy individuals, and it has much lower biological activity than insulin. Clinically, elevated proinsulin levels or an increased proinsulin-to-insulin ratio can indicate beta-cell stress or dysfunction and are observed in type 2 diabetes, obesity-related insulin resistance, and certain insulinomas.

The INS gene encodes proinsulin, and its proper processing is essential for normal glucose homeostasis. Proinsulin serves as a biomarker and a therapeutic precursor in research and clinical settings.