Proinsulin

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Insulin undergoes extensive posttranslational modification along the production pathway. Production and secretion are largely independent; prepared insulin is stored awaiting secretion. Both C-peptide and mature insulin are biologically active. Cell components and proteins in this image are not to scale.

Proinsulin is the prohormone precursor to insulin made in the beta cell of the islets of Langerhans. It is synthesized in the 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, where it is processed by a series of proteases to form mature insulin. Mature insulin has 39 less amino acids; 4 are removed altogether, and the remaining 35 form the C-peptide. The C-peptide is abstracted from the center of the proinsulin sequence; the two other ends (the B chain and A chain) remain connected by disulfide bonds.

When insulin is purified from bovine or porcine pancreas, all the proinsulin is not fully removed. When some people use these insulins, the proinsulin can cause the body to react with a rash, to resist the insulin, or even to make dents or lumps in the skin at the place where the insulin is injected. In some type 1 diabetics, the autoimmune response which destroyed the islets of Langerhans acted against proinsulin, making them more susceptible to this sort of a side effect. However, sometimes the iatrogenic immune response comes from slight differences between bovine, porcine and human insulin itself.de:Proinsulin