Proinsulin

Proinsulin is a protein and a precursor to insulin produced by the pancreas. It is synthesized in the pancreatic beta cells and is crucial in the regulation of glucose metabolism.

Structure

Proinsulin is a single-chain polypeptide consisting of 86 amino acids. It has three domains: an A-chain, a B-chain, and a connecting peptide known as the C-peptide. The A and B chains are connected by disulfide bonds, while the C-peptide is excised during the conversion of proinsulin to insulin.

Synthesis and Secretion

The synthesis of proinsulin begins in the rough endoplasmic reticulum (RER) where it is initially produced as preproinsulin. Preproinsulin is then converted into proinsulin in the RER lumen. Proinsulin is packaged into secretory vesicles in the Golgi apparatus, where it is converted into insulin and C-peptide. These are then secreted into the bloodstream in response to an increase in blood glucose levels.

Function

Proinsulin itself has minimal insulin activity. Its primary function is to serve as a precursor to insulin. The conversion of proinsulin to insulin and C-peptide is a critical step in the regulation of glucose metabolism. The C-peptide is also believed to have biological activity, including the promotion of vasodilation and sodium excretion.

Clinical Significance

Abnormal proinsulin levels can be indicative of various medical conditions. Elevated proinsulin levels can be seen in conditions such as type 2 diabetes, insulinoma, and polycystic ovary syndrome. Proinsulin testing is used in the diagnosis and management of these conditions.

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  Pathway of insulin production

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  Structure of proinsulin

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  Annotated diagram of proinsulin

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  Evolution of proinsulin