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 - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue EBioMedicine Année : 2020

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

Eleni Georgiadou
  • Fonction : Auteur
  • PersonId : 783025
  • IdRef : 182271803
Serge Luquet
Raphael Scharfmann

Résumé

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.
Fichier principal
Vignette du fichier
1-s2.0-S235239642030270X-main.pdf (5.37 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

hal-02939141 , version 1 (15-09-2020)

Identifiants

Citer

Chloé Amouyal, Julien Castel, Claudiane Guay, Amélie Lacombe, Jessica Denom, et al.. 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, 2020, 58, pp.102895. ⟨10.1016/j.ebiom.2020.102895⟩. ⟨hal-02939141⟩
84 Consultations
91 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More