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Abstract

Insulin is synthesized in the pancreatic beta cell via a series of precursor proteins which include preproinsulin and proinsulin. Preproinsulin carries additional information to target the nascent protein chain into the endoplasmic reticulum (ER) where, after cleavage of the signal peptide, it folds efficiently to assume the native proinsulin structure stabilized by three disulfide bonds. The beta-cell ER appears to be especially adapted to supporting these processes in the face of varying demands for the hormone. However, sustained high-level stimulation of insulin biosynthesis, as in diabetes, may result in beta-cell damage or death via ER stress mechanisms. Correctly folded proinsulin is transferred to the Golgi apparatus from which it is efficiently sorted into secretory vesicles of the regulated pathway, where it is converted to insulin and C-peptide. These peptides, along with others such as Islet Amyloid Polypeptide (IAPP/amylin) and various other granin family peptides, are all stored in highly organized mature secretory vesicles/granules, awaiting their regulated discharge into the bloodstream on demand. More information is needed on many aspects of insulin biosynthesis, particularly its regulatory mechanisms and the pathological processes that influence their function.

Keywords

Beta Cell Endoplasmic Reticulum Stress Secretory Granule Trans Golgi Cisternal Network Islet Amyloid Polypeptide 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • Donald F. Steiner
    • 1
  1. 1.Department of Biochemistry and Molecular BiologyThe University of ChicagoChicagoUSA

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