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Insulin is synthesized in significant quantities only in beta cells in the pancreas. Since it is a protein or a polypeptide structure it is synthesized like most other proteins via transcription and translation of DNA into mRNA and amino acid chains or polypeptide chains. Thereafter the protein undergoes structural changes to achieve its final form.
The insulin mRNA is translated as a single chain precursor called preproinsulin. Thereafter the removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin.
Proinsulin consists of three domains:
In the endoplasmic reticulum the proinsulin is exposed to several specific endopeptidases which excise the C peptide. This forms the mature form of insulin. Insulin and free C peptide are packed in the Golgi bodies into secretory granules which accumulate in the cytoplasm.
When the beta cell is appropriately stimulated, insulin is secreted from the cell by exocytosis. The insulin then diffuses into small blood vessels of the pancreas. C peptide is also secreted into blood, but has no known biological activity.
Insulin synthesis is regulated by several mechanisms. These include:
Insulin is secreted in primarily in response to elevated blood concentrations of glucose. Thus insulin is secreted as the body detects high blood glucose and helps regulate the levels of glucose. There are some other stimuli like sight and taste of food, increased blood levels of amino acids and fatty acids that may also promote the release of insulin.
The steps in regulation of insulin release include:
During digestion (around one or two hours following a meal), insulin release is not continuous, but occurs in bursts. The oscillations occur within a period of 3–6 minutes and result in changes of blood insulin levels from more than ~800 pmol/l to less than 100 pmol/l.
After the insulin acts on its receptor site it may be released back into the extracellular environment, or it may be degraded by the cell. Degradation involves intake or engulfing (endocytosis) of the insulin-receptor complex followed by the action of insulin degrading enzyme.
The degradation mainly takes place in the liver. An insulin molecule produced by the beta cells of the pancreas is degraded within approximately one hour after its initial release into circulation.