%0 Journal Article %A Pérez Arana, Gonzalo Martín %A Díaz Gómez, Alfredo Luis %A Bancalero-de los Reyes, José %A Camacho Ramírez, Alonso %A Fernández Vivero, José %A Ribelles García, Antonio %A Almorza Gomar, David %A Carrasco Molinillo, María del Carmen %A Mateo-Gavira, Isabel %A Prada Oliveira, José Arturo %T The long-term failure of RYGB surgery in improving T2DM is related to hyperinsulinism. %D 2021 %@ 1618-0402 %U http://hdl.handle.net/10498/25823 %X BACKGROUND: Roux-en-Y gastric bypass (RYGB) is the gold standard method for bariatric surgery and leads to substantial improvements in Type 2 Diabetes mellitus. However, many patients experience relapses in diabetes five years after undergoing this aggressive surgical procedure. We focus on beta-cell population changes and absorptive intestinal consequences after RYGB in a healthy nonobese animal model after a long survival period. METHODS: For our purpose, we use three groups of Wistar rats: RYGB-operated, surgical control (Sham) and fasting control. We measure alpha-, beta-cell mass; transcription (Arx, and Pdx-1) and proliferation (Ki67) factors; glucose tolerance and insulin release after oral glucose tests; histological adaptive changes in the jejunum; and intestinal glucose transporters. RESULTS: Our results showed an early increase in insulin secretion after surgery, that decrease at the end of the study. The beta-cell mass reduces twenty-four weeks after RYGB, which coincides with decrease of Pdx-1 transcription promoter factor. These was coincident with an increase in alpha-mass and a high expression of Arx in RYGB group. CONCLUSIONS: The analysis of all data showed beta-cell mass transdifferentiation into alpha-cell mass in RYGB rats. Due to long-term exhaustion of the beta-cell population by hyperinsulinism derived from digestive tract adaptation to surgery. Copyright © 2021 The Author(s). Published by Elsevier GmbH.. All rights reserved. %K Alpha-Cells %K Beta-Cell mass %K Pancreas %K Type 2 Diabetes mellitus %K Roux-en Y-gastric bypass %K Incretins %K Cellular differentiation %~ Universidad de Cádiz