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AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress

Chronic exposure of pancreatic β-cells to elevated nutrient levels impairs their function and potentially induces apoptosis. Like in other cell types, AMPK is activated in β-cells under conditions of nutrient deprivation, while little is known on AMPK responses to metabolic stresses. Here, we first...

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Autores principales: Brun, Thierry, Jiménez-Sánchez, Cecilia, Madsen, Jesper Grud Skat, Hadadi, Noushin, Duhamel, Dominique, Bartley, Clarissa, Oberhauser, Lucie, Trajkovski, Mirko, Mandrup, Susanne, Maechler, Pierre
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312098/
https://www.ncbi.nlm.nih.gov/pubmed/32492936
http://dx.doi.org/10.3390/ijms21113982
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author Brun, Thierry
Jiménez-Sánchez, Cecilia
Madsen, Jesper Grud Skat
Hadadi, Noushin
Duhamel, Dominique
Bartley, Clarissa
Oberhauser, Lucie
Trajkovski, Mirko
Mandrup, Susanne
Maechler, Pierre
author_facet Brun, Thierry
Jiménez-Sánchez, Cecilia
Madsen, Jesper Grud Skat
Hadadi, Noushin
Duhamel, Dominique
Bartley, Clarissa
Oberhauser, Lucie
Trajkovski, Mirko
Mandrup, Susanne
Maechler, Pierre
author_sort Brun, Thierry
collection PubMed
description Chronic exposure of pancreatic β-cells to elevated nutrient levels impairs their function and potentially induces apoptosis. Like in other cell types, AMPK is activated in β-cells under conditions of nutrient deprivation, while little is known on AMPK responses to metabolic stresses. Here, we first reviewed recent studies on the role of AMPK activation in β-cells. Then, we investigated the expression profile of AMPK pathways in β-cells following metabolic stresses. INS-1E β-cells and human islets were exposed for 3 days to glucose (5.5–25 mM), palmitate or oleate (0.4 mM), and fructose (5.5 mM). Following these treatments, we analyzed transcript levels of INS-1E β-cells by qRT-PCR and of human islets by RNA-Seq; with a special focus on AMPK-associated genes, such as the AMPK catalytic subunits α1 (Prkaa1) and α2 (Prkaa2). AMPKα and pAMPKα were also evaluated at the protein level by immunoblotting. Chronic exposure to the different metabolic stresses, known to alter glucose-stimulated insulin secretion, did not change AMPK expression, either in insulinoma cells or in human islets. Expression profile of the six AMPK subunits was marginally modified by the different diabetogenic conditions. However, the expression of some upstream kinases and downstream AMPK targets, including K-ATP channel subunits, exhibited stress-specific signatures. Interestingly, at the protein level, chronic fructose treatment favored fasting-like phenotype in human islets, as witnessed by AMPK activation. Collectively, previously published and present data indicate that, in the β-cell, AMPK activation might be implicated in the pre-diabetic state, potentially as a protective mechanism.
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spelling pubmed-73120982020-06-25 AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress Brun, Thierry Jiménez-Sánchez, Cecilia Madsen, Jesper Grud Skat Hadadi, Noushin Duhamel, Dominique Bartley, Clarissa Oberhauser, Lucie Trajkovski, Mirko Mandrup, Susanne Maechler, Pierre Int J Mol Sci Article Chronic exposure of pancreatic β-cells to elevated nutrient levels impairs their function and potentially induces apoptosis. Like in other cell types, AMPK is activated in β-cells under conditions of nutrient deprivation, while little is known on AMPK responses to metabolic stresses. Here, we first reviewed recent studies on the role of AMPK activation in β-cells. Then, we investigated the expression profile of AMPK pathways in β-cells following metabolic stresses. INS-1E β-cells and human islets were exposed for 3 days to glucose (5.5–25 mM), palmitate or oleate (0.4 mM), and fructose (5.5 mM). Following these treatments, we analyzed transcript levels of INS-1E β-cells by qRT-PCR and of human islets by RNA-Seq; with a special focus on AMPK-associated genes, such as the AMPK catalytic subunits α1 (Prkaa1) and α2 (Prkaa2). AMPKα and pAMPKα were also evaluated at the protein level by immunoblotting. Chronic exposure to the different metabolic stresses, known to alter glucose-stimulated insulin secretion, did not change AMPK expression, either in insulinoma cells or in human islets. Expression profile of the six AMPK subunits was marginally modified by the different diabetogenic conditions. However, the expression of some upstream kinases and downstream AMPK targets, including K-ATP channel subunits, exhibited stress-specific signatures. Interestingly, at the protein level, chronic fructose treatment favored fasting-like phenotype in human islets, as witnessed by AMPK activation. Collectively, previously published and present data indicate that, in the β-cell, AMPK activation might be implicated in the pre-diabetic state, potentially as a protective mechanism. MDPI 2020-06-01 /pmc/articles/PMC7312098/ /pubmed/32492936 http://dx.doi.org/10.3390/ijms21113982 Text en © 2020 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 Article
Brun, Thierry
Jiménez-Sánchez, Cecilia
Madsen, Jesper Grud Skat
Hadadi, Noushin
Duhamel, Dominique
Bartley, Clarissa
Oberhauser, Lucie
Trajkovski, Mirko
Mandrup, Susanne
Maechler, Pierre
AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress
title AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress
title_full AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress
title_fullStr AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress
title_full_unstemmed AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress
title_short AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress
title_sort ampk profiling in rodent and human pancreatic beta-cells under nutrient-rich metabolic stress
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312098/
https://www.ncbi.nlm.nih.gov/pubmed/32492936
http://dx.doi.org/10.3390/ijms21113982
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