Cargando…

Glucagon Receptor Signaling and Glucagon Resistance

Hundred years after the discovery of glucagon, its biology remains enigmatic. Accurate measurement of glucagon has been essential for uncovering its pathological hypersecretion that underlies various metabolic diseases including not only diabetes and liver diseases but also cancers (glucagonomas). T...

Descripción completa

Detalles Bibliográficos
Autores principales: Janah, Lina, Kjeldsen, Sasha, Galsgaard, Katrine D., Winther-Sørensen, Marie, Stojanovska, Elena, Pedersen, Jens, Knop, Filip K., Holst, Jens J., Wewer Albrechtsen, Nicolai J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651628/
https://www.ncbi.nlm.nih.gov/pubmed/31284506
http://dx.doi.org/10.3390/ijms20133314
_version_ 1783438391417765888
author Janah, Lina
Kjeldsen, Sasha
Galsgaard, Katrine D.
Winther-Sørensen, Marie
Stojanovska, Elena
Pedersen, Jens
Knop, Filip K.
Holst, Jens J.
Wewer Albrechtsen, Nicolai J.
author_facet Janah, Lina
Kjeldsen, Sasha
Galsgaard, Katrine D.
Winther-Sørensen, Marie
Stojanovska, Elena
Pedersen, Jens
Knop, Filip K.
Holst, Jens J.
Wewer Albrechtsen, Nicolai J.
author_sort Janah, Lina
collection PubMed
description Hundred years after the discovery of glucagon, its biology remains enigmatic. Accurate measurement of glucagon has been essential for uncovering its pathological hypersecretion that underlies various metabolic diseases including not only diabetes and liver diseases but also cancers (glucagonomas). The suggested key role of glucagon in the development of diabetes has been termed the bihormonal hypothesis. However, studying tissue-specific knockout of the glucagon receptor has revealed that the physiological role of glucagon may extend beyond blood-glucose regulation. Decades ago, animal and human studies reported an important role of glucagon in amino acid metabolism through ureagenesis. Using modern technologies such as metabolomic profiling, knowledge about the effects of glucagon on amino acid metabolism has been expanded and the mechanisms involved further delineated. Glucagon receptor antagonists have indirectly put focus on glucagon’s potential role in lipid metabolism, as individuals treated with these antagonists showed dyslipidemia and increased hepatic fat. One emerging field in glucagon biology now seems to include the concept of hepatic glucagon resistance. Here, we discuss the roles of glucagon in glucose homeostasis, amino acid metabolism, and lipid metabolism and present speculations on the molecular pathways causing and associating with postulated hepatic glucagon resistance.
format Online
Article
Text
id pubmed-6651628
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-66516282019-08-08 Glucagon Receptor Signaling and Glucagon Resistance Janah, Lina Kjeldsen, Sasha Galsgaard, Katrine D. Winther-Sørensen, Marie Stojanovska, Elena Pedersen, Jens Knop, Filip K. Holst, Jens J. Wewer Albrechtsen, Nicolai J. Int J Mol Sci Review Hundred years after the discovery of glucagon, its biology remains enigmatic. Accurate measurement of glucagon has been essential for uncovering its pathological hypersecretion that underlies various metabolic diseases including not only diabetes and liver diseases but also cancers (glucagonomas). The suggested key role of glucagon in the development of diabetes has been termed the bihormonal hypothesis. However, studying tissue-specific knockout of the glucagon receptor has revealed that the physiological role of glucagon may extend beyond blood-glucose regulation. Decades ago, animal and human studies reported an important role of glucagon in amino acid metabolism through ureagenesis. Using modern technologies such as metabolomic profiling, knowledge about the effects of glucagon on amino acid metabolism has been expanded and the mechanisms involved further delineated. Glucagon receptor antagonists have indirectly put focus on glucagon’s potential role in lipid metabolism, as individuals treated with these antagonists showed dyslipidemia and increased hepatic fat. One emerging field in glucagon biology now seems to include the concept of hepatic glucagon resistance. Here, we discuss the roles of glucagon in glucose homeostasis, amino acid metabolism, and lipid metabolism and present speculations on the molecular pathways causing and associating with postulated hepatic glucagon resistance. MDPI 2019-07-05 /pmc/articles/PMC6651628/ /pubmed/31284506 http://dx.doi.org/10.3390/ijms20133314 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Janah, Lina
Kjeldsen, Sasha
Galsgaard, Katrine D.
Winther-Sørensen, Marie
Stojanovska, Elena
Pedersen, Jens
Knop, Filip K.
Holst, Jens J.
Wewer Albrechtsen, Nicolai J.
Glucagon Receptor Signaling and Glucagon Resistance
title Glucagon Receptor Signaling and Glucagon Resistance
title_full Glucagon Receptor Signaling and Glucagon Resistance
title_fullStr Glucagon Receptor Signaling and Glucagon Resistance
title_full_unstemmed Glucagon Receptor Signaling and Glucagon Resistance
title_short Glucagon Receptor Signaling and Glucagon Resistance
title_sort glucagon receptor signaling and glucagon resistance
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651628/
https://www.ncbi.nlm.nih.gov/pubmed/31284506
http://dx.doi.org/10.3390/ijms20133314
work_keys_str_mv AT janahlina glucagonreceptorsignalingandglucagonresistance
AT kjeldsensasha glucagonreceptorsignalingandglucagonresistance
AT galsgaardkatrined glucagonreceptorsignalingandglucagonresistance
AT winthersørensenmarie glucagonreceptorsignalingandglucagonresistance
AT stojanovskaelena glucagonreceptorsignalingandglucagonresistance
AT pedersenjens glucagonreceptorsignalingandglucagonresistance
AT knopfilipk glucagonreceptorsignalingandglucagonresistance
AT holstjensj glucagonreceptorsignalingandglucagonresistance
AT weweralbrechtsennicolaij glucagonreceptorsignalingandglucagonresistance