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PMID: 1769434 Published · ppublish English Journal Article Review

Structural domains and molecular lifestyles of insulin and its precursors in the pancreatic beta cell.

Diabetologia ·Vol. 34 ·No. 11 ·1991-11-00 ·Pages 767-78

Halban PA

Abstract

Insulin is both produced and degraded within the pancreatic Beta cell. Production involves the synthesis of the initial insulin precursor preproinsulin, which is converted to proinsulin shortly after (or during) translocation into the lumen of the rough endoplasmic reticulum. Proinsulin is then transported to the trans-cisternae of the Golgi complex where it is directed towards nascent secretory granules. Conversion of proinsulin to insulin and C-peptide arises within secretory granules, and is dependent upon their acidification. Granule contents are discharged by exocytosis in response to an appropriate stimulus. This represents the regulated secretory pathway to which more than 99% of proinsulin is directed in Beta cells of a healthy individual. An alternative route also exists in the Beta cell, the constitutive secretory pathway. It involves the rapid transfer of products from the Golgi complex to the plasma membrane for immediate release, with, it is supposed, little occasion for prohormone conversion. Even if delivered appropriately to secretory granules, not all insulin is released; some is degraded by fusion of granules with lysosomes (crinophagy). Each event in the molecular lifestyles of insulin and its precursors in the Beta cell will be seen to be governed by their own discrete functional domains. The identification and characterisation of these protein domains will help elucidate the steps responsible for delivery of proinsulin to secretory granules and conversion to insulin. Understanding the molecular mechanism of these steps may, in turn, help to explain defective insulin production in certain disease states including diabetes mellitus.

MeSH Terms
Animals C-Peptide/metabolism Humans Hyperinsulinism/metabolism Insulin/genetics,metabolism Insulin Secretion Islets of Langerhans/metabolism Proinsulin/metabolism Protein Precursors/metabolism
Chemicals
C-Peptide Insulin Protein Precursors preproinsulin Proinsulin
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Halban P A
Laboratoires de Recherche Louis Jeantet, University of Geneva Medical Centre, Switzerland.
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Article Info
Journal
Diabetologia
Abbr.
Diabetologia
ISSN
0012-186X
DOI
10.1007/BF00408349
Published
1991-11-00
Pages
767-78
Language
English
Region
Germany
NLM ID
0006777
Subset
IM
External Links
PubMed source DOI: 10.1007/BF00408349 View journal details
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