Insulin Chemistry and Synthesis

Insulin is a small protein; human insulin has a molecular weight of 5808. It is composed of two amino acid
chains, connected to each other by disulfide linkages.

When the two amino acid chains are split apart, the functional activity of the insulin molecule is lost. Insulin is synthesized in the beta cells by the usual cell machinery for protein synthesis, beginning with translation of the insulin RNA by ribosomes attached to the endoplasmic reticulum to form an  insulin preprohormone.

 This initial preprohormone has a molecular weight of about 11,500, but it is then cleaved in the endoplasmic reticulum to form a  proinsulin with a molecular weight of about 9000; most of this is further cleaved in the Golgi apparatus to form insulin and peptide fragments before being packaged in the secretory granules.

However, about one sixth of the final secreted product is still in the form of proinsulin.The proinsulin has virtually no insulin activity.When insulin is secreted into the blood, it circulates almost entirely in an unbound form; it has a plasma half-life that averages only about 6 minutes, so that it is mainly cleared from the circulation within 10 to 15 minutes.

Except for that portion of the insulin that combines with receptors in the target cells, the remainder is degraded by the enzyme insulinase mainly in the liver, to a lesser extent in the kidneys and muscles, and slightly in most other tissues. This rapid removal from the plasma is important, because, at times, it is as important to turn off rapidly as to turn on the control functions of insulin.

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