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Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion

OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. He...

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Autores principales: Leloup, Corinne, Tourrel-Cuzin, Cécile, Magnan, Christophe, Karaca, Melis, Castel, Julien, Carneiro, Lionel, Colombani, Anne-Laure, Ktorza, Alain, Casteilla, Louis, Pénicaud, Luc
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646066/
https://www.ncbi.nlm.nih.gov/pubmed/19073765
http://dx.doi.org/10.2337/db07-1056
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author Leloup, Corinne
Tourrel-Cuzin, Cécile
Magnan, Christophe
Karaca, Melis
Castel, Julien
Carneiro, Lionel
Colombani, Anne-Laure
Ktorza, Alain
Casteilla, Louis
Pénicaud, Luc
author_facet Leloup, Corinne
Tourrel-Cuzin, Cécile
Magnan, Christophe
Karaca, Melis
Castel, Julien
Carneiro, Lionel
Colombani, Anne-Laure
Ktorza, Alain
Casteilla, Louis
Pénicaud, Luc
author_sort Leloup, Corinne
collection PubMed
description OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase from 5.5 to 16.7 mmol/l stimulated ROS generation, which was reversed by antioxidants. Insulin secretion was dose dependently blunted by antioxidants and highly correlated with ROS levels. The incapacity of β-cells to secrete insulin in response to glucose with antioxidants was associated with a decrease in ROS production and in contrast to the maintenance of high levels of ATP and NADH. Then, we investigated the mitochondrial origin of ROS (mROS) as the triggering signal. Insulin release was mimicked by the mitochondrial-complex blockers, antimycin and rotenone, that generate mROS. The adding of antioxidants to mitochondrial blockers or to glucose was used to lower mROS reversed insulin secretion. Finally, calcium imaging on perifused islets using glucose stimulation or mitochondrial blockers revealed that calcium mobilization was completely reversed using the antioxidant trolox and that it was of extracellular origin. No toxic effects were present using these pharmacological approaches. CONCLUSIONS—Altogether, these complementary results demonstrate that mROS production is a necessary stimulus for glucose-induced insulin secretion.
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spelling pubmed-26460662010-03-01 Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion Leloup, Corinne Tourrel-Cuzin, Cécile Magnan, Christophe Karaca, Melis Castel, Julien Carneiro, Lionel Colombani, Anne-Laure Ktorza, Alain Casteilla, Louis Pénicaud, Luc Diabetes Islet Studies OBJECTIVE—Insulin secretion involves complex events in which the mitochondria play a pivotal role in the generation of signals that couple glucose detection to insulin secretion. Studies on the mitochondrial generation of reactive oxygen species (ROS) generally focus on chronic nutrient exposure. Here, we investigate whether transient mitochondrial ROS production linked to glucose-induced increased respiration might act as a signal for monitoring insulin secretion. RESEARCH DESIGN AND METHODS—ROS production in response to glucose was investigated in freshly isolated rat islets. ROS effects were studied using a pharmacological approach and calcium imaging. RESULTS—Transient glucose increase from 5.5 to 16.7 mmol/l stimulated ROS generation, which was reversed by antioxidants. Insulin secretion was dose dependently blunted by antioxidants and highly correlated with ROS levels. The incapacity of β-cells to secrete insulin in response to glucose with antioxidants was associated with a decrease in ROS production and in contrast to the maintenance of high levels of ATP and NADH. Then, we investigated the mitochondrial origin of ROS (mROS) as the triggering signal. Insulin release was mimicked by the mitochondrial-complex blockers, antimycin and rotenone, that generate mROS. The adding of antioxidants to mitochondrial blockers or to glucose was used to lower mROS reversed insulin secretion. Finally, calcium imaging on perifused islets using glucose stimulation or mitochondrial blockers revealed that calcium mobilization was completely reversed using the antioxidant trolox and that it was of extracellular origin. No toxic effects were present using these pharmacological approaches. CONCLUSIONS—Altogether, these complementary results demonstrate that mROS production is a necessary stimulus for glucose-induced insulin secretion. American Diabetes Association 2009-03 /pmc/articles/PMC2646066/ /pubmed/19073765 http://dx.doi.org/10.2337/db07-1056 Text en Copyright © 2009, American Diabetes Association Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Islet Studies
Leloup, Corinne
Tourrel-Cuzin, Cécile
Magnan, Christophe
Karaca, Melis
Castel, Julien
Carneiro, Lionel
Colombani, Anne-Laure
Ktorza, Alain
Casteilla, Louis
Pénicaud, Luc
Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion
title Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion
title_full Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion
title_fullStr Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion
title_full_unstemmed Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion
title_short Mitochondrial Reactive Oxygen Species Are Obligatory Signals for Glucose-Induced Insulin Secretion
title_sort mitochondrial reactive oxygen species are obligatory signals for glucose-induced insulin secretion
topic Islet Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646066/
https://www.ncbi.nlm.nih.gov/pubmed/19073765
http://dx.doi.org/10.2337/db07-1056
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