Insulin Synthesis

The processing and transport of intermediates that occur during the synthesis of insulin are shown in Figures 1B and 2. Biosynthesis involves production of two inactive precursors, preproinsulin and proinsulin, which are sequentially cleaved to form the active hormone plus the connecting or C-peptide in a 1:1 ratio (see Fig. 2). [Note: The Cpeptide is essential for proper insulin folding. Also, because its half-life in plasma is longer than that of insulin, the C-peptide level is a good indicator of insulin production and secretion.] Insulin is stored in cytosolic granules that, given the proper stimulus , are released by exocytosis. 

Insulin is degraded by insulin-degrading enzyme, which is present in the liver and, to a lesser extent, in the kidneys. Insulin has a plasma half-life of ~6 minutes. This short duration of action permits rapid changes in circulating levels of the hormone.

Figure 1:  A. Structure of insulin. B. Formation of human insulin from preproinsulin. S-S = disulfide bond.

Figure 2:  Intracellular movements of insulin and its precursors. mRNA = messenger RNA; RER = rough endoplasmic reticulum.