Proinsulin is the prohormone precursor to insulin made in the beta cells of the Pancreatic Islets, specialized regions of the pancreas.

[3] However, because proinsulin has a longer half life than insulin, it can account for anywhere from 5–30% of the insulin-like structures circulating in the blood.

[3] Proinsulin is the final single chain protein structure secreted by cells before cleavage into mature insulin.

[8] Proinsulin is synthesized on membrane associated ribosomes found on the rough endoplasmic reticulum, where it is folded and its disulfide bonds are oxidized.

It is then transported to the Golgi apparatus where it is packaged into secretory vesicles, and where it is processed by a series of proteases to form mature insulin.

Mature insulin has 35 fewer amino acids; 4 are removed altogether, and the remaining 31 form the C-peptide.

[citation needed] The post translational modification of proinsulin to mature insulin only occurs in the beta cells of the pancreatic islets.

[19] Additional problems with proinsulin that can lead to diabetes include mutations in the number of cysteines present, which could affect correct folding.

[9] If the mutation causes only a mild change it could simply stress the endoplasmic reticulum’s ability to properly fold the protein.

[20] Regulation of the concentration of proinsulin during embryonic development is crucial, as too much or too little of the peptide can cause defects and death of the fetus.