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The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror

Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, s...

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Autores principales: Martínez, María Sofía, Manzano, Alexander, Olivar, Luis Carlos, Nava, Manuel, Salazar, Juan, D’Marco, Luis, Ortiz, Rina, Chacín, Maricarmen, Guerrero-Wyss, Marion, Cabrera de Bravo, Mayela, Cano, Clímaco, Bermúdez, Valmore, Angarita, Lisse
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431704/
https://www.ncbi.nlm.nih.gov/pubmed/34502413
http://dx.doi.org/10.3390/ijms22179504
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author Martínez, María Sofía
Manzano, Alexander
Olivar, Luis Carlos
Nava, Manuel
Salazar, Juan
D’Marco, Luis
Ortiz, Rina
Chacín, Maricarmen
Guerrero-Wyss, Marion
Cabrera de Bravo, Mayela
Cano, Clímaco
Bermúdez, Valmore
Angarita, Lisse
author_facet Martínez, María Sofía
Manzano, Alexander
Olivar, Luis Carlos
Nava, Manuel
Salazar, Juan
D’Marco, Luis
Ortiz, Rina
Chacín, Maricarmen
Guerrero-Wyss, Marion
Cabrera de Bravo, Mayela
Cano, Clímaco
Bermúdez, Valmore
Angarita, Lisse
author_sort Martínez, María Sofía
collection PubMed
description Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (K(ATP)) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.
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spelling pubmed-84317042021-09-11 The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror Martínez, María Sofía Manzano, Alexander Olivar, Luis Carlos Nava, Manuel Salazar, Juan D’Marco, Luis Ortiz, Rina Chacín, Maricarmen Guerrero-Wyss, Marion Cabrera de Bravo, Mayela Cano, Clímaco Bermúdez, Valmore Angarita, Lisse Int J Mol Sci Review Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (K(ATP)) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy. MDPI 2021-09-01 /pmc/articles/PMC8431704/ /pubmed/34502413 http://dx.doi.org/10.3390/ijms22179504 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Martínez, María Sofía
Manzano, Alexander
Olivar, Luis Carlos
Nava, Manuel
Salazar, Juan
D’Marco, Luis
Ortiz, Rina
Chacín, Maricarmen
Guerrero-Wyss, Marion
Cabrera de Bravo, Mayela
Cano, Clímaco
Bermúdez, Valmore
Angarita, Lisse
The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
title The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
title_full The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
title_fullStr The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
title_full_unstemmed The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
title_short The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror
title_sort role of the α cell in the pathogenesis of diabetes: a world beyond the mirror
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431704/
https://www.ncbi.nlm.nih.gov/pubmed/34502413
http://dx.doi.org/10.3390/ijms22179504
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