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Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes

Pancreatic beta‐cells are central regulators of glucose homeostasis. By tightly coupling nutrient sensing and granule exocytosis, beta‐cells adjust the secretion of insulin to the circulating blood glucose levels. Failure of beta‐cells to augment insulin secretion in insulin‐resistant individuals le...

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Autores principales: De Marchi, Umberto, Fernandez‐Martinez, Silvia, de la Fuente, Sergio, Wiederkehr, Andreas, Santo‐Domingo, Jaime
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246559/
https://www.ncbi.nlm.nih.gov/pubmed/32056196
http://dx.doi.org/10.1111/bph.15018
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author De Marchi, Umberto
Fernandez‐Martinez, Silvia
de la Fuente, Sergio
Wiederkehr, Andreas
Santo‐Domingo, Jaime
author_facet De Marchi, Umberto
Fernandez‐Martinez, Silvia
de la Fuente, Sergio
Wiederkehr, Andreas
Santo‐Domingo, Jaime
author_sort De Marchi, Umberto
collection PubMed
description Pancreatic beta‐cells are central regulators of glucose homeostasis. By tightly coupling nutrient sensing and granule exocytosis, beta‐cells adjust the secretion of insulin to the circulating blood glucose levels. Failure of beta‐cells to augment insulin secretion in insulin‐resistant individuals leads progressively to impaired glucose tolerance, Type 2 diabetes, and diabetes‐related diseases. Mitochondria play a crucial role in β‐cells during nutrient stimulation, linking the metabolism of glucose and other secretagogues to the generation of signals that promote insulin secretion. Mitochondria are double‐membrane organelles containing numerous channels allowing the transport of ions across both membranes. These channels regulate mitochondrial energy production, signalling, and cell death. The mitochondria of β‐cells express ion channels whose physio/pathological role is underappreciated. Here, we describe the mitochondrial ion channels identified in pancreatic β‐cells, we further discuss the possibility of targeting specific β‐cell mitochondrial channels for the treatment of Type 2 diabetes, and we finally highlight the evidence from clinical studies. LINKED ARTICLES: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
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spelling pubmed-82465592021-07-02 Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes De Marchi, Umberto Fernandez‐Martinez, Silvia de la Fuente, Sergio Wiederkehr, Andreas Santo‐Domingo, Jaime Br J Pharmacol Cellular Metabolism and Diseases ‐ Review Articles Pancreatic beta‐cells are central regulators of glucose homeostasis. By tightly coupling nutrient sensing and granule exocytosis, beta‐cells adjust the secretion of insulin to the circulating blood glucose levels. Failure of beta‐cells to augment insulin secretion in insulin‐resistant individuals leads progressively to impaired glucose tolerance, Type 2 diabetes, and diabetes‐related diseases. Mitochondria play a crucial role in β‐cells during nutrient stimulation, linking the metabolism of glucose and other secretagogues to the generation of signals that promote insulin secretion. Mitochondria are double‐membrane organelles containing numerous channels allowing the transport of ions across both membranes. These channels regulate mitochondrial energy production, signalling, and cell death. The mitochondria of β‐cells express ion channels whose physio/pathological role is underappreciated. Here, we describe the mitochondrial ion channels identified in pancreatic β‐cells, we further discuss the possibility of targeting specific β‐cell mitochondrial channels for the treatment of Type 2 diabetes, and we finally highlight the evidence from clinical studies. LINKED ARTICLES: This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc John Wiley and Sons Inc. 2020-03-21 2021-05 /pmc/articles/PMC8246559/ /pubmed/32056196 http://dx.doi.org/10.1111/bph.15018 Text en © 2020 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Cellular Metabolism and Diseases ‐ Review Articles
De Marchi, Umberto
Fernandez‐Martinez, Silvia
de la Fuente, Sergio
Wiederkehr, Andreas
Santo‐Domingo, Jaime
Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes
title Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes
title_full Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes
title_fullStr Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes
title_full_unstemmed Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes
title_short Mitochondrial ion channels in pancreatic β‐cells: Novel pharmacological targets for the treatment of Type 2 diabetes
title_sort mitochondrial ion channels in pancreatic β‐cells: novel pharmacological targets for the treatment of type 2 diabetes
topic Cellular Metabolism and Diseases ‐ Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246559/
https://www.ncbi.nlm.nih.gov/pubmed/32056196
http://dx.doi.org/10.1111/bph.15018
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