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

• Main Authors: Amouyal, Chloé, Castel, Julien, Guay, Claudiane, Lacombe, Amélie, Denom, Jessica, Migrenne-Li, Stéphanie, Rouault, Christine, Marquet, Florian, Georgiadou, Eleni, Stylianides, Theodoros, Luquet, Serge, Le Stunff, Hervé, Scharfmann, Raphael, Clément, Karine, Rutter, Guy A., Taboureau, Olivier, Magnan, Christophe, Regazzi, Romano, Andreelli, Fabrizio
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2021
• Subjects: Science::Medicine; Diabetes; Bariatric Surgery
• Online Access: https://hdl.handle.net/10356/148805
• Institution: Nanyang Technological University

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.