The biological activity of glucagon has recently been proposed to both stimulate hepatic glucose production and also include a paradoxical insulinotropic effect, which could suggest a new role of glucagon in the pathophysiology type 2 diabetes mellitus (T2DM). An insulinotropic role of glucagon has been observed after bariatric/metabolic surgery that is mediated through the GLP-1 receptor on pancreatic beta cells. This effect appears to be modulated by other members of the proglucagon family, playing a key role in the beneficial effects and complications of bariatric/metabolic surgery. Glucagon serves a dual role after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). In addition to maintaining blood glucose levels, glucagon exhibits an insulinotropic effect, suggesting that glucagon has a more complex function than simply an “anti-insulin hormone”.
Background. Sleeve gastrectomy (SG) is one of the most commonly performed bariatric surgeries is able to treat diabetes (T2DM) better than many drugs. The mechanisms that underlie this phenomenon remains unclear. We propose that somatostatin (SST), isoforms, SST-14 and SST-28, are key to explaining the pathophysiological mechanisms behind T2DM improvement after SG. Methods. We underwent surgeries on three groups of Wistar rats -fasting (FC), surgery control (Sham), and SG groups-. We measured plasma levels of glucose, insulin, SST-14 and SS-28 at several weeks after surgery, islet somatostatin receptor (SSTR) and cell populations at short and long-term after surgery. We performed a Pasireotide (SST-28 analogue) infusion assay in another group of rats to confirm the influence of SST-28 plasma levels on the delta-cell population. Results. We found an elevation of the insulin response after surgery in SG animals but a decrease in insulin response in the long-term with a loss of beta cell mass. An increase in duodenal SST-28-producing cells in the duodenum and a loss of pancreatic SST-14-producing cells was measured after SG but not in controls. The expression of SSTR-5 in delta-cell populations from every group and the ability of the Pasireotide infusion assay to decrease the delta-cell population indicate the effect of SST-28 plasma levels on delta-cell maintenance. Conclusion. After SG begins with a compensatory response in the duodenum, the depletion of beta cell mass after losing the brake that constitutes SST-14 at the paracrine level. This process may explain the percentage of T2DM relapse after SG.
RESUMEN: Numerosas hipótesis se invocan para explicar el efecto beneficioso sobre el metabolismo glucídico tras la cirugía bariátrica. Algunos autores abogan por la secreción y liberación de distintas sustancias con funciones endocrinas (enterohormonas). Una de las sustancias más señaladas como efector, con efectos contrastados pero datos controvertidos, es el GLP-1. Nuestro estudio se realizó en ratas Wistar macho sanas, para evitar la ausencia de factores de confusión como son la DMT2 y la obesidad. Para conocer el mapa de adaptación a la secreción de GLP-1 tras la cirugía, se designaron 5 grupos: dos grupos control (de ayuno y de estrés quirúrgico); y tres grupos quirúrgicos (gastrectomía vertical, resección del 50 % del intestino medio y el Bypass gástrico con montaje en Y de Roux). Después de tres meses se estudiaron mediante técnicas inmunohistoquímicas el patrón de síntesis de GLP-1 en las distintas porciones del intestino delgado. También se estudió la expresión de los receptores de membrana en las células de los islotes pancreáticos. Se observó la existencia de un significativo aumento del número de células secretoras en íleon, duodeno y yeyuno en los grupos quirúrgicos de técnicas mixtas (RYGB) y malabsortivas (RI50). Igualmente se observó una elevación de los receptores pancreáticos en las mismas técnicas frente a los controles. Nuestros datos indican que la secreción intestinal de GLP-1 y su sensibilidad a nivel pancreáticas están aumentada, como efecto adaptativo a la agresión mecánica del tubo y a la alteración del flujo de nutrientes tras la cirugía.
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