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

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...

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Published in:Annals of anatomy 2022-02, Vol.240, p.151855-151855, Article 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: Article
Language:English
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
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Summary: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.
ISSN:0940-9602
1618-0402
DOI:10.1016/j.aanat.2021.151855