Insulin Synthesis and Secretion

 

Structure of Insulin
  • Relatively a small protein, with a molecular weight of about 6000 Daltons.

  • Composed of two chains held together by disulfide bonds.
Biosynthesis of Insulin
  • The insulin mRNA is translated as a single chain precursor called preproinsulin, and removal of its signal peptide during insertion into the endoplasmic reticulum generates proinsulin.

  • Within the endoplasmic reticulum, proinsulin is exposed to several specific endopeptidases which excise the C peptide, thereby generating the mature form of insulin.

  • Insulin and free C peptide are packaged in the Golgi into secretory granules which accumulate in the cytoplasm. When the B cell is appropriately stimulated, insulin is secreted from the cell by exocytosis and diffuses into islet capillary blood.

Control of Insulin Secretion
  • Secreted primarily in response to elevated blood concentrations of glucose.

  • Neural stimuli (e.g. site and taste of food) and increased blood concentrations of other fuel molecules, including amino acids and fatty acids, also promote insulin secretion.

  • It is thought that elaevated glucose levels within the B cell leads to membrane depolarization and an influx of extracellular calcium. The resulting increase in intracellular calcium is thought to be one of the primary triggers for exocytosis of insulin-containing secretory granules.