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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| Language: | English |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/11/3982 |
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| author | Thierry Brun Cecilia Jiménez-Sánchez Jesper Grud Skat Madsen Noushin Hadadi Dominique Duhamel Clarissa Bartley Lucie Oberhauser Mirko Trajkovski Susanne Mandrup Pierre Maechler |
| author_facet | Thierry Brun Cecilia Jiménez-Sánchez Jesper Grud Skat Madsen Noushin Hadadi Dominique Duhamel Clarissa Bartley Lucie Oberhauser Mirko Trajkovski Susanne Mandrup Pierre Maechler |
| author_sort | Thierry Brun |
| collection | DOAJ |
| 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 (<i>Prkaa1</i>) and α2 (<i>Prkaa2</i>). 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. |
| first_indexed | 2024-03-10T19:26:56Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:26:56Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9493167bf8f04c5db20c0fd4b34b87be2023-11-20T02:31:03ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012111398210.3390/ijms21113982AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic StressThierry Brun0Cecilia Jiménez-Sánchez1Jesper Grud Skat Madsen2Noushin Hadadi3Dominique Duhamel4Clarissa Bartley5Lucie Oberhauser6Mirko Trajkovski7Susanne Mandrup8Pierre Maechler9Department of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandDepartment of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandFunctional Genomics and Metabolism Research Unit, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandDepartment of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandDepartment of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandDepartment of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandDepartment of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandFunctional Genomics and Metabolism Research Unit, Department of Biochemistry and Molecular Biology, University of Southern Denmark, 5230 Odense, DenmarkDepartment of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, SwitzerlandChronic 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 (<i>Prkaa1</i>) and α2 (<i>Prkaa2</i>). 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.https://www.mdpi.com/1422-0067/21/11/3982AMPKATPfructosepancreatic isletsbeta-cellinsulin |
| spellingShingle | Thierry Brun Cecilia Jiménez-Sánchez Jesper Grud Skat Madsen Noushin Hadadi Dominique Duhamel Clarissa Bartley Lucie Oberhauser Mirko Trajkovski Susanne Mandrup Pierre Maechler AMPK Profiling in Rodent and Human Pancreatic Beta-Cells under Nutrient-Rich Metabolic Stress International Journal of Molecular Sciences AMPK ATP fructose pancreatic islets beta-cell insulin |
| 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 | AMPK ATP fructose pancreatic islets beta-cell insulin |
| url | https://www.mdpi.com/1422-0067/21/11/3982 |
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