The Endocrine Pancreas & Glucose Control

proinsulin

Proinsulin is insulin still wearing its scaffolding. The beta cell first makes a single long chain in which the future insulin's two pieces are joined by a connecting segment. That connector folds the molecule correctly and lines up the disulfide bonds, like a temporary brace that holds two beams in place while the joints set.

After folding, enzymes cut proinsulin at two points, releasing mature insulin and freeing the connecting piece as C-peptide. Equal numbers of insulin and C-peptide molecules are stored in secretory granules and released together. Proinsulin itself is the prohormone stage in this assembly line, preceded by an even earlier preproinsulin that carried a signal sequence.

A small amount of intact and partially processed proinsulin normally escapes into the blood. An elevated proinsulin-to-insulin ratio signals beta cells under strain, releasing immature granules, and is seen in type 2 diabetes and beta-cell dysfunction — a useful clue that processing capacity is being outstripped.