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The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective

Enteroglucagon refers to the predominant peptide with glucagon-like immunoreactivity (GLI) that is released by the intestine into the circulation in response to nutrients. Development of a radioimmunoassay for glucagon revealed issues that were not apparent in applications of the insulin radioimmuno...

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Autor principal: Conlon, J. Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226317/
https://www.ncbi.nlm.nih.gov/pubmed/34177808
http://dx.doi.org/10.3389/fendo.2021.683089
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author Conlon, J. Michael
author_facet Conlon, J. Michael
author_sort Conlon, J. Michael
collection PubMed
description Enteroglucagon refers to the predominant peptide with glucagon-like immunoreactivity (GLI) that is released by the intestine into the circulation in response to nutrients. Development of a radioimmunoassay for glucagon revealed issues that were not apparent in applications of the insulin radioimmunoassay. The fact that some antisera raised against glucagon recognized glucagon-related peptides in extracts of both pancreas and gut whereas others recognized only components in the pancreas remained a mystery until it was realized that the “gut GLI cross-reactive” antisera were directed against an epitope in the N-terminal to central region of glucagon whereas the “pancreatic glucagon specific” antisera were directed against an epitope in the C-terminal region. Unlike the cross-reactive antisera, the glucagon specific antisera did not recognize components in which glucagon was extended from its C-terminus by additional amino acids. Initial attempts to purify enteroglucagon from porcine ileum led to the erroneous conclusion that enteroglucagon comprised 100 amino acids with an apparent molecular mass of 12,000 Da and was consequently given the name glicentin. Subsequent work established that the peptide constituted residues (1-69) of proglucagon (M(r) 8128()). In the 40 years since the structural characterization of glicentin, attempts to establish an unambiguous physiological function for enteroglucagon have not been successful. Unlike the oxyntomodulin domain at the C-terminus of enteroglucagon, the primary structure of the N-terminal domain (glicentin-related pancreatic peptide) has been poorly conserved among mammals. Consequently, most investigations of the bioactivity of porcine glicentin may have been carried out in inappropriate animal models. Enteroglucagon may simply represent an inactive peptide that ensures that the intestine does not release equimolar amounts of a hyperglycemic agent (glucagon) and a hypoglycemic agent (GLP-1) after ingestion of nutrients.
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spelling pubmed-82263172021-06-26 The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective Conlon, J. Michael Front Endocrinol (Lausanne) Endocrinology Enteroglucagon refers to the predominant peptide with glucagon-like immunoreactivity (GLI) that is released by the intestine into the circulation in response to nutrients. Development of a radioimmunoassay for glucagon revealed issues that were not apparent in applications of the insulin radioimmunoassay. The fact that some antisera raised against glucagon recognized glucagon-related peptides in extracts of both pancreas and gut whereas others recognized only components in the pancreas remained a mystery until it was realized that the “gut GLI cross-reactive” antisera were directed against an epitope in the N-terminal to central region of glucagon whereas the “pancreatic glucagon specific” antisera were directed against an epitope in the C-terminal region. Unlike the cross-reactive antisera, the glucagon specific antisera did not recognize components in which glucagon was extended from its C-terminus by additional amino acids. Initial attempts to purify enteroglucagon from porcine ileum led to the erroneous conclusion that enteroglucagon comprised 100 amino acids with an apparent molecular mass of 12,000 Da and was consequently given the name glicentin. Subsequent work established that the peptide constituted residues (1-69) of proglucagon (M(r) 8128()). In the 40 years since the structural characterization of glicentin, attempts to establish an unambiguous physiological function for enteroglucagon have not been successful. Unlike the oxyntomodulin domain at the C-terminus of enteroglucagon, the primary structure of the N-terminal domain (glicentin-related pancreatic peptide) has been poorly conserved among mammals. Consequently, most investigations of the bioactivity of porcine glicentin may have been carried out in inappropriate animal models. Enteroglucagon may simply represent an inactive peptide that ensures that the intestine does not release equimolar amounts of a hyperglycemic agent (glucagon) and a hypoglycemic agent (GLP-1) after ingestion of nutrients. Frontiers Media S.A. 2021-06-11 /pmc/articles/PMC8226317/ /pubmed/34177808 http://dx.doi.org/10.3389/fendo.2021.683089 Text en Copyright © 2021 Conlon https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Conlon, J. Michael
The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective
title The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective
title_full The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective
title_fullStr The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective
title_full_unstemmed The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective
title_short The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective
title_sort enigmatic n-terminal domain of proglucagon; a historical perspective
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226317/
https://www.ncbi.nlm.nih.gov/pubmed/34177808
http://dx.doi.org/10.3389/fendo.2021.683089
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