A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice
Background: Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our...
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Elsevier
2020-08-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S235239642030270X |
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doaj-46ade57e556a4d639af37af56b46d965 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chloé Amouyal Julien Castel Claudiane Guay Amélie Lacombe Jessica Denom Stéphanie Migrenne-Li Christine Rouault Florian Marquet Eleni Georgiadou Theodoros Stylianides Serge Luquet Hervé Le Stunff Raphael Scharfmann Karine Clément Guy A. Rutter Olivier Taboureau Christophe Magnan Romano Regazzi Fabrizio Andreelli |
spellingShingle |
Chloé Amouyal Julien Castel Claudiane Guay Amélie Lacombe Jessica Denom Stéphanie Migrenne-Li Christine Rouault Florian Marquet Eleni Georgiadou Theodoros Stylianides Serge Luquet Hervé Le Stunff Raphael Scharfmann Karine Clément Guy A. Rutter Olivier Taboureau Christophe Magnan Romano Regazzi Fabrizio Andreelli A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice EBioMedicine Diabetes Bariatric surgery Beta cell function Insulin secretion microRNA ob/ob mouse |
author_facet |
Chloé Amouyal Julien Castel Claudiane Guay Amélie Lacombe Jessica Denom Stéphanie Migrenne-Li Christine Rouault Florian Marquet Eleni Georgiadou Theodoros Stylianides Serge Luquet Hervé Le Stunff Raphael Scharfmann Karine Clément Guy A. Rutter Olivier Taboureau Christophe Magnan Romano Regazzi Fabrizio Andreelli |
author_sort |
Chloé Amouyal |
title |
A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice |
title_short |
A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice |
title_full |
A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice |
title_fullStr |
A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice |
title_full_unstemmed |
A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice |
title_sort |
surrogate of roux-en-y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2020-08-01 |
description |
Background: Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our aim was to identify pathways, evident in the islet transcriptome, that characterize the adaptive response to bariatric surgery independently of body weight changes. Methods: We performed entero-gastro-anastomosis (EGA) with pyloric ligature in leptin-deficient ob/ob mice as a surrogate of Roux-en-Y gastric bypass (RYGB) in humans. Multiple approaches such as determination of glucose tolerance, GLP-1 and insulin secretion, whole body insulin sensitivity, ex vivo glucose-stimulated insulin secretion (GSIS) and functional multicellular Ca2+-imaging, profiling of mRNA and of miRNA expression were utilized to identify significant biological processes involved in pancreatic islet recovery. Findings: EGA resolved diabetes, increased pancreatic insulin content and GSIS despite a persistent increase in fat mass, systemic and intra-islet inflammation, and lipotoxicity. Surgery differentially regulated 193 genes in the islet, most of which were involved in the regulation of glucose metabolism, insulin secretion, calcium signaling or beta cell viability, and these were normalized alongside changes in glucose metabolism, intracellular Ca2+ dynamics and the threshold for GSIS. Furthermore, 27 islet miRNAs were differentially regulated, four of them hubs in a miRNA-gene interaction network and four others part of a blood signature of diabetes resolution in ob/ob mice and in humans. Interpretation: Taken together, our data highlight novel miRNA-gene interactions in the pancreatic islet during the resolution of diabetes after bariatric surgery that form part of a blood signature of diabetes reversal. Funding: European Union's Horizon 2020 research and innovation programme via the Innovative Medicines Initiative 2 Joint Undertaking (RHAPSODY), INSERM, Société Francophone du Diabète, Institut Benjamin Delessert, Wellcome Trust Investigator Award (212625/Z/18/Z), MRC Programme grants (MR/R022259/1, MR/J0003042/1, MR/L020149/1), Diabetes UK (BDA/11/0004210, BDA/15/0005275, BDA 16/0005485) project grants, National Science Foundation (310030–188447), Fondation de l'Avenir. |
topic |
Diabetes Bariatric surgery Beta cell function Insulin secretion microRNA ob/ob mouse |
url |
http://www.sciencedirect.com/science/article/pii/S235239642030270X |
work_keys_str_mv |
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doaj-46ade57e556a4d639af37af56b46d9652020-11-25T03:53:11ZengElsevierEBioMedicine2352-39642020-08-0158102895A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob miceChloé Amouyal0Julien Castel1Claudiane Guay2Amélie Lacombe3Jessica Denom4Stéphanie Migrenne-Li5Christine Rouault6Florian Marquet7Eleni Georgiadou8Theodoros Stylianides9Serge Luquet10Hervé Le Stunff11Raphael Scharfmann12Karine Clément13Guy A. Rutter14Olivier Taboureau15Christophe Magnan16Romano Regazzi17Fabrizio Andreelli18Sorbonne Université, INSERM, Nutrition and Obesities; Systemic approaches (NutriOmics), Paris, France; AP-HP, Pitié-Salpêtrière Hospital, Diabetology department, F-75013 Paris, FranceUniversité de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, FranceDepartment of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005, Lausanne, SwitzerlandPreclinICAN, Institute of Cardiometabolism and Nutrition, Paris, FranceUniversité de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, FranceUniversité de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, FranceSorbonne Université, INSERM, Nutrition and Obesities; Systemic approaches (NutriOmics), Paris, FranceSorbonne Université, INSERM, Nutrition and Obesities; Systemic approaches (NutriOmics), Paris, FranceSection of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UKLoughborough University, Loughborough, UKUniversité de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, FranceUniversité de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, FranceUniversité de Paris, Cochin Institute, Inserm U1016, Paris 75014, FranceSorbonne Université, INSERM, Nutrition and Obesities; Systemic approaches (NutriOmics), Paris, France; APHP, Pitié-Salpêtrière Hospital, Nutrition department, F-75013 Paris, FranceSection of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK; Lee Kong Chian School of Medicine, Nan Yang Technological University, SingaporeUniversité de Paris, BFA, Team CMPLI, Inserm U1133, CNRS UMR 8251, Paris, France.Université de Paris, BFA, UMR 8251, CNRS, F-75013 Paris, FranceDepartment of Fundamental Neurosciences, University of Lausanne, Rue du Bugnon 9, CH-1005, Lausanne, Switzerland; Department of Biomedical Sciences, University of Lausanne, Rue du Bugnon 7, CH-1005 Lausanne, SwitzerlandSorbonne Université, INSERM, Nutrition and Obesities; Systemic approaches (NutriOmics), Paris, France; AP-HP, Pitié-Salpêtrière Hospital, Diabetology department, F-75013 Paris, France; Corresponding author at: AP-HP, Pitié-Salpêtrière Hospital, Diabetology department, F-75013 Paris, France.Background: Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our aim was to identify pathways, evident in the islet transcriptome, that characterize the adaptive response to bariatric surgery independently of body weight changes. Methods: We performed entero-gastro-anastomosis (EGA) with pyloric ligature in leptin-deficient ob/ob mice as a surrogate of Roux-en-Y gastric bypass (RYGB) in humans. Multiple approaches such as determination of glucose tolerance, GLP-1 and insulin secretion, whole body insulin sensitivity, ex vivo glucose-stimulated insulin secretion (GSIS) and functional multicellular Ca2+-imaging, profiling of mRNA and of miRNA expression were utilized to identify significant biological processes involved in pancreatic islet recovery. Findings: EGA resolved diabetes, increased pancreatic insulin content and GSIS despite a persistent increase in fat mass, systemic and intra-islet inflammation, and lipotoxicity. Surgery differentially regulated 193 genes in the islet, most of which were involved in the regulation of glucose metabolism, insulin secretion, calcium signaling or beta cell viability, and these were normalized alongside changes in glucose metabolism, intracellular Ca2+ dynamics and the threshold for GSIS. Furthermore, 27 islet miRNAs were differentially regulated, four of them hubs in a miRNA-gene interaction network and four others part of a blood signature of diabetes resolution in ob/ob mice and in humans. Interpretation: Taken together, our data highlight novel miRNA-gene interactions in the pancreatic islet during the resolution of diabetes after bariatric surgery that form part of a blood signature of diabetes reversal. Funding: European Union's Horizon 2020 research and innovation programme via the Innovative Medicines Initiative 2 Joint Undertaking (RHAPSODY), INSERM, Société Francophone du Diabète, Institut Benjamin Delessert, Wellcome Trust Investigator Award (212625/Z/18/Z), MRC Programme grants (MR/R022259/1, MR/J0003042/1, MR/L020149/1), Diabetes UK (BDA/11/0004210, BDA/15/0005275, BDA 16/0005485) project grants, National Science Foundation (310030–188447), Fondation de l'Avenir.http://www.sciencedirect.com/science/article/pii/S235239642030270XDiabetesBariatric surgeryBeta cell functionInsulin secretionmicroRNAob/ob mouse |