Glucagon-Producing Cell Expansion in Wistar Rats. Changes to Islet Architecture After Sleeve Gastrectomy

Purpose Many studies about bariatric surgery have analyzed the effect of sleeve gastrectomy (SG) on glucose improvement, beta-cell mass, and islet size modification. The effects of SG on the other endocrine cells of the pancreas, such as the alpha-cell population, and their regulatory mechanisms remain less studied. Materials and Methods We focused our work on the changes in the alpha-cell population after SG in a healthy model of Wistar rats. We measured alpha-cell mass, glucose tolerance, and insulin release after oral glucose tolerance tests and plasma glucagon secretion patterns after insulin infusion. Three Wistar rat groups were employed: SG-operated, surgical control (Sham), and fasting control. Results The results obtained showed significant increases in the alpha-cell population after SG. The result was an increase in beta-cell transdifferentiation; it was shown by some expressed molecules (the loss of expression of Pdx-1 and the increase in Arx and Pax6 cells/mm(2) of islet). The serum results were enhanced plasma glucagon secretion pattern after insulin infusion assays and normal glucose tolerance and insulin release after OGTT. Conclusion We concluded that SG leads to an expansion of the alpha-cell population, at expense of beta-cell; this expansion of alpha-cells is related to transdifferentiation. Plasma glucose level was not affected due to an increased glucagon response

Somatostatin: From a supporting actor to the protagonist to explain the long-term effect of sleeve gastrectomy on glucose metabolism.

BACKGROUND: Bariatric/metabolic surgery has become the most effective treatment against type 2 Diabetes mellitus (T2DM). The role of many gastrointestinal hormones in T2DM has been proposed, but the pathophysiological models described vary greatly depending on the anatomical rearrangements after surgery. We focus on somatostatin as a common factor in two of the most commonly performed surgical procedures in a healthy rodent model. We performed sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and also an experimental surgery without gastric involvement (intestinal resection of 50 % jejunum-ileum portion -IR50 %). METHODS: We used five groups of Wistar rats: fasting control, sham-operated, SG-operated, RYGB-operated and IR50-operated. We analysed several parameters 4 and 23 weeks after surgery: plasma SST-14/28 fractions, plasma glucose, insulin release and SST-producing cell expression in the duodenum and pancreatic islets. RESULTS: Numerous SST-producing cells in the duodenum but a low number in the pancreas and a long-term loss of glucose tolerance were observed in SG and RYGB animals. Additionally, a high plasma SST-28 fraction was found in animals after SG but not after RYGB. Finally, IR50 animals showed no differences versus controls. CONCLUSIONS: In our SG model the amplitude of insulin response after metabolic surgeries, is mediated by SST-28 plasma levels derived from the proportional compensatory effect of gastric SST-producing tissue ablation. In addition, a strong compensatory response to the surgical loss of gastric SST-producing cells, leads to long-term loss of insulin production after SG but not in the others. Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved

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

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

Comportamiento de células endocrinas periféricas en ratas wistar: cambios en la arquitectura del islote pancreático tras la gastrectomía vertical

La obesidad y la diabetes interesan especialmente por sus complicaciones de carácter prevenible. La RYGB es la técnica quirúrgica de referencia, sin embargo la gastrectomía vertical (SG) se está haciendo cada vez más habitual por su baja invasividad, facilidad por abordaje laparoscópico y menor número de complicaciones. Tras observarse la remisión de la diabetes tras la cirugía bariátrica, esta se ha propuesto como cirugía metabólica. La beta es la célula de referencia en el contexto de la remisión de la diabetes, existiendo casi ausencia de estudios sobre la célula alfa. Consideramos, podría ser un mecanismo plausible subyacente en la remisión de la diabetes. Motivo por el que nuestro objetivo fundamental ha sido analizar la microanatomia e interrelación funcional endocrina pancreática, específicamente reseñando cambios a nivel celular alfa, inducidos por la SG. Para ello se han valorado la ganancia de peso postquirúrgica, la tolerancia glucémica ante un test de sobrecarga, la masa beta intergrupo, el test de inyección intraperitoneal de insulina y la respuesta de glucagón. Igualmente se estudió en base molecular a la expresión de Arx, Pax6 y PDX-1 los hallazgos encontrados como factores críticos para cada tipo celular. La ganancia de peso, mostró una tendencia similar entre los grupos, con aparición de diferencias estadísticas de forma tardía, con menor ganancia en el grupo experimental, confirmándose la presencia de cambios metabólicos precedentes. La ausencia de intolerancia glucémica como ocurre tras otras técnicas quirúrgicas, puede corresponderse con la preservación del tubo digestivo. De hecho, observamos tras la infusión de insulina intraperitoneal que la curva glucémica se mantuvo estable en el grupo experimental, lo que evidencia una compensación más que adecuada en los animales intervenidos por SG. La respuesta glucagonémica más adecuada en el grupo experimental, se correspondió con los posibles cambios a nivel pancreático a nivel de la célula alfa. Dada la ausencia de diferencia en la masa beta intergrupo y dados los hallazgos encontrados a nivel de los factores de transcripción críticos para cada tipo celular, consideramos la cirugía tipo SG induce un fenómeno de hiperplasia celular alfa secundaria a un proceso de transdiferenciación celular beta a alfa. Estos hallazgos se basaron en la determinación de factores de transcripción de linaje celular tipo beta y alfa. Encontrando los marcadores de madurez alfa normofuncionante elevados y un aumento de masa alfa sin mayor proliferación, se concluye que el fenómeno subyacente es una hiperplasia secundaria a transdiferenciación beta a alfa. En este sentido, subrayamos que el descenso de PDX-1 con el mantenimiento de la masa beta intergrupo puede tener varias justificaciones que exponemos en nuestro trabajo. A pesar de que la hiperplasia alfa se ha asociado como ?perpetuadora de la propia diabetes? por algunos autores, otros han planteado ésta como un mecanismo compensador o respuesta adaptativa. Destacamos que una base uni o bidireccional del mecanismo de transdiferenciación, podría ser el fundamento por el cual mediante el primer fenómeno pudiera ser un mecanismo perpetuador de la diabetes. Sin embargo, mediante la estimulación quirúrgica con cambios no solo locales y de forma controlada, pueda producirse un evento bidireccional con reposición beta posterior. Esta idea tiene sustento sobre la hipótesis beta>alfa>beta ya planteada por otros autores

Sleeve Gastrectomy and Roux-En-Y Gastric Bypass. Two Sculptors of the Pancreatic Islet

Several surgical procedures are performed for the treatment of obesity. A main outcome of these procedures is the improvement of type 2 diabetes mellitus. Trying to explain this, gastrointestinal hormone levels and their effect on organs involved in carbohydrate metabolism, such as liver, gut, muscle or fat, have been studied intensively after bariatric surgery. These effects on endocrine-cell populations in the pancreas have been less well studied. We gathered the existing data on these pancreatic-cell populations after the two most common types of bariatric surgery, the sleeve gastrectomy (SG) and the roux-en-Y gastric bypass (RYGB), with the aim to explain the pathophysiological mechanisms underlying these surgeries and to improve their outcome