The long-term failure of RYGB surgery in improving T2DM is related to hyperinsulinism

• Published in: Annals of anatomy Vol. 240; p. 151855
• Main Authors: Pérez-Arana, Gonzalo-Martín, Gómez, Alfredo Díaz, de los Reyes, José Bancalero, Camacho-Ramírez, Alonso, Fernández-Vivero, José, Ribelles-García, Antonio, Almorza-Gomar, David, Carrasco-Molinillo, Carmen, Mateo-Gavira, Isabel, Prada-Oliveira, José-Arturo
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.02.2022
• Subjects: Alpha-Cells; Animals; Beta-Cell mass; Blood Glucose; Cellular differentiation; Diabetes Mellitus, Type 2; Gastric Bypass; Humans; Hyperinsulinism; Incretins; Insulin Resistance; Pancreas; Rats; Rats, Wistar; Roux-en Y-gastric bypass; Type 2 Diabetes mellitus; Incretins; Beta-Cell mass; Alpha-Cells; Pancreas; Cellular differentiation; Type 2 Diabetes mellitus; Roux-en Y-gastric bypass
• ISSN: 0940-9602; 1618-0402
• DOI: 10.1016/j.aanat.2021.151855

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. 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. 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. 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.