Effects of preduodenal ileal surgical transposition on enteroendocrine intestinal cells in wistar rats: Histomorphological and serum changes.

In our study, we focused on the role of the distal ileum as a main endocrine actor in relation to the pancreas. We investigated the effects of intestinally released hormones on the pancreas in terms of type 2 diabetes mellitus (T2DM) improvement, as a main effect of bariatric surgeries. To specifically study the importance of the ileum, we used an experimental surgical model performed in healthy Wistar rats. After preduodenal transposition of the ileum, we analyzed the histology and enterohormonal cells of the intestine. We measured the plasma level of several hormones and effectors in this enteropancreatic axis. We used a surgical control (Sham) group and a surgical group, where ileum preduodenal transposition (PDIT) was performed. We measured basal glycemia and serum levels of several incretins, including GLP-1, PYY, and GIP, and we performed a glucose overdose test. After two test periods, the basal glycemia and glucose overdose results were not different between groups, however, the PDIT group had significantly increased expression of GLP-1, with increased cellular release in the ileum and duodenum compared with the Sham group. Both plasma GIP levels and GIP tissue expression were decreased in the PDIT group compared with the sham group. There were no differences in PPY hormone levels. The ileum crypts and villi of the PDIT group showed improvement in histological parameters. We concluded that model animals had an altered transposed ileum related to the enterohormonal adaptation of the ileum. Our results indicated that the ileum is important in the hormonal control of the enteropancreatic axis.

Somatostatin: a possible mediator of the long-term effects of experimental vertical gastrectomy on glucose metabolism in rats?

BACKGROUND: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric surgeries. SG treats type 2 diabetes mellitus better than several drugs. The mechanisms that underlie this phenomenon are not clear. This study proposed that somatostatin (SST) isoforms SST-14 and SST-28 are key in the carbohydrate after SG. METHODS: Surgeries were performed on 3 groups of Wistar rats: the fasting, surgery control, and SG groups. Plasma levels of glucose, insulin, SST-14, and SST-28 were measured at 2 survival periods after surgery. Islet SST receptor (SSTR) and cell populations were studied. 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: This study found an elevation in the insulin response after SG in animals but a decrease in the insulin response over 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 were observed after SG in animals but not in controls. The expression of SSTR type 5 in delta-cell populations from each group and the ability of the pasireotide infusion assay to decrease the delta-cell population indicated the effect of SST-28 plasma levels on delta-cell maintenance. CONCLUSION: After SG initiates a compensatory response in the duodenum, beta-cell mass is depleted after loss of the brake that regulates SST-14 at the paracrine level in a nonobese, normoglycemic rat model. This was an experimental model, with no clinical translation to the human clinic, with a preliminary importance regarding new pathophysiologic perspectives or pathways.

Lymphoepithelial cyst of the pancreas.

Within pancreatic cysts, the lymphoepithelial variant is considered a highly atypical condition with few reported cases in the literature. Following a case managed in our hospital, we aim to shed more light on this entity as an incidental finding, providing a temporal description until its excision, along with radiological, surgical, and histological images.

Dual effect of RYGB on the entero-insular axis: How GLP-1 is enhanced by surgical duodenal exclusion.

BACKGROUND: The role of the ileum and Glucagon Like Peptide-1 (GLP-1) secretion in the pathophysiological processes underlying the effects of Roux-en-Y gastric bypass (RYGB) on type 2 Diabetes mellitus (T2DM) improvement has been previously determined. However, the roles of duodenal exclusion and Glucose Insulinotropic Peptide (GIP) secretion change is not clear. To clarify this aspect, we compared the pathophysiological mechanisms triggered by RYGB, which implies the early arrival of food to the ileum with duodenal exclusion, and through pre-duodenal ileal transposition (PdIT), with early arrival of food to the ileum but without duodenal exclusion, in a nondiabetic rodent model. METHODS: We compared plasma and insulin, glucose (OGTT), GIP and GLP-1 plasma levels, ileal and duodenal GIP and GLP-1 tissue expression and beta-cell mass for n = 12 Sham-operated, n = 6 RYGB-operated, and n = 6 PdIT-operated Wistar rats. RESULTS: No surgery induced changes in blood glucose levels after the OGTT. However, RYGB induced a significant and strong insulin response that increased less in PdIT animals. Increased beta-cell mass was found in RYGB and PdIT animals as well as similar GLP-1 secretion and GLP-1 intestinal expression. However, differential GIP secretion and GIP duodenal expression were found between RYGB and PdIT. CONCLUSION: The RYGB effect on glucose metabolism is mostly due to early ileal stimulation; however, duodenal exclusion potentiates the ileal response within RYGB effects through enhanced GIP secretion.

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.

Beta-cell mass adaptation to ileum nutrient flow. An experimental model.

The population with obesity has increased at an alarming rate during this century. Bariatric surgery has been demonstrated to be a good method to control weight and, most importantly, associated comorbidities, such as type 2 diabetes mellitus or high blood pressure. The reason why this happens even before losing significant weight remains unclear. Many authors believe that incretins play a main role, triggering special functions of the digestive tract. In reports, these hypotheses are known as foregut and hindgut theories. Initially, the theories were mutually exclusive; additionally, many other propositions have been analysed, according to different surgical techniques (e.g., bile acids and specific enterohormonal components). To elucidate the participation of the ileum, we developed a surgical technique to study the rapid response to nutrients in the ileum. Our goal was to study the stress functional test and histological changes in the pancreas that may explain the variations in glycaemic homeostasis in our rat model. After the oral glucose tolerance test, the experimental group presented an increased insulin release response with conserved glycaemia. We report an increasing beta-cell mass in the experimental group (+11.87 mg vs. +9.65 mg, respectively), while alpha-cell mass was not different. Based on transcription factors, the pathways that were increased were the proliferation process (as the number of PCNA-positive cells in the experimental group versus sham (+12.06 vs. +6.2 PCNA+ cells/mm²)) and transdifferentiation (ARX; +2.67 ARX+ cells/mm² in the experimental group vs. +2.04 ARX+ cells/mm² in the controls). We report the consequences of the rapid arrival of nonprocessed nutrients to the ileum on the endocrine cellular pancreas. The ileum could be a principal effector in the enterohormonal axis, which conditions endocrine pancreas cellularity.

The influence of massive jejunectomy on endocrine pancreas of diabetic Goto-Kakizaki.

OBJECTIVE: Several bariatric surgeries have been related to the T2DM improvement in obese patients. Despite the different mechanism invoked for this improvement, many evidences showed that the pancreas cellularity is conditioned for the homeostatic physiological changes after these surgeries. Many authors reported the changes in beta-cell mass after some surgeries in healthy rats. We purpose to analyze the changes in ß-cell cellularity and ß-cell-mass after a severe malabsorptive surgical method. Thus, we studied several parameters of the islet morphometric composition after a massive jejunal resection. MATERIALS AND METHODS: We employed Goto-Kakizaki diabetic non-obese rats, which underwent the 50% resection of middle portion of the jejunum versus a control group. After 3 months, rats were sacrificed and pancreas was immunohistochemicaly studied. RESULTS: The ß-cell mass was analyzed and several parameters about the endocrine islet size distribution were studied. We report an increase of ß-cell mass in massive resection surgical group versus controls. The islet distribution was significant different between both groups. Endocrine islets of surgical group were bigger with a different cellular distribution. CONCLUSION: According to the enteroendocrine changes related to surgeries in jejunum, as in other gastrointestinal portions, the cellularity of islets changes as an adaptive process to glycemic demands.

OBJETIVO: Varias técnicas quirúrgicas bariátricas han sido relacionadas con el mejoramiento de la T2DM en pacientes obesos. Se han invocado distintos mecanismos de porqué se da este mejoramiento y muchas evidencias apuntan a que la celularidad del páncreas cambia por las condiciones fisiológicas tras estas cirugías. Se han publicado cambios en la celularidad beta en ratas sanas sometidas a estos procesos. Y nos proponemos observar dichos cambios en ratas diabéticas tras una resección jejunal masiva. Estudiamos varios parámetros sobre la masa beta y la morfometría de los islotes, que indiquen los procesos celulares que han tenido lugar. MATERIAL Y METODO: Empleamos Goto-Kakizaki, un modelo de rata diabética no obesa, a la que se sometió a una resección del 50%de la poción media del yeyuno. Tras tres meses de supervivencia, las ratas se estudiaron los páncreas mediante inmunocitoquímica. RESULTADOS: Mostramos un incremento de la masa beta en las ratas resecadas frente a los controles. La distribución de islotes fue significativamente distinta entre los grupos, donde los islotes eran mayores en las ratas diabéticas. CONCLUSIÓN: Los cambios glucémicos tras las resecciones masivas yeyunales cambian la celularidad del páncreas como una muestra de la capacidad adaptativa del mismo a las modificaciones.

Peptide Tyrosine-Tyrosine Triggers GLP-2-Mediated Intestinal Hypertrophy After Roux-en-Y Gastric Bypass.

PURPOSE : Intestinal remodeling and adaptation of the alimentary limb after Roux-en-Y gastric bypass (RYGB) play an important role in the pathophysiological events that lead to type 2 diabetes mellitus (T2DM) improvement. Intestinal absorptive loop hypertrophy and growth following surgery have been related to GLP-2 secretion by ileal L-cells. The secretion of peptide tyrosine-tyrosine (PYY) enterohormone after a meal has been proposed as a trigger for ileal secretion of GLP-1. Our aim is to determine the role of PYY as a GLP-2 secretion modulator as an adaptation result in the alimentary limb after RYGB. METHOD: We used a non-obese euglycemic rodent model. Circulating glucose, insulin, PYY, and GLP-2 were measured in the experimental and control groups. We used four groups: fasting control, Sham-operated, RYGB-operated (RYGB), and RYGB-operated and treated with BIIE0246 (RYGB + BII). BIIE0246 is a NPY2 receptor antagonist in L-cells. Intestinal glucose transporters and GLP-1 and PYY gut expression and hypertrophy were analyzed after 12 weeks of surgery. RESULTS: RYGB increased PYY3-36 plasma levels in rats with or without BII treatment. A high-insulin response was observed in the RYGB group but not in the control or RYGB + BII groups. BIIE0246 treatment limited plasma GLP-2 levels. In the alimentary intestinal limb, hypertrophy and SGLT1 and GLUT1 expression appeared to be reduced after RYGB compared to controls. CONCLUSION: The postprandial ileal PYY secretion is enhanced after RYGB. This increase mediates GLP-2 release through its binding to the Y2 receptor on L-cells. This mechanism plays a role in alimentary limb hypertrophy after surgery.

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.

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.

From conventional two-stage hepatectomy to ALPPS: Fifteen years of experience in a hepatobiliary surgery unit.

BACKGROUND: Hepatectomy in patients with large tumor load may result in postoperative liver failure and associated complications due to excessive liver parenchyma removal. Conventional two-stage hepatectomy (TSH) and associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) technique are possible solutions to this problem. Colorectal liver metastases (CRLM) is the most frequent indication, and there is a need to assess outcomes for both techniques to improve surgical and long-term oncological outcomes in these patients. METHODS: A single-center retrospective study was designed to compare TSH with ALPPS in patients with initially unresectable bilateral liver tumors between January 2005 and January 2020. ALPPS was performed from January 2012 onwards as the technique of choice. Long-term overall survival (OS) and disease-free survival (DFS) were evaluated as primary outcome in CRLM patients. Postoperative morbidity, mortality and liver growth in all patients were also evaluated. RESULTS: A total of 38 staged hepatectomies were performed: 17 TSH and 21 ALPPS. Complete resection rate was 76.5% (n = 13) in the TSH group and 85.7% (n = 18) in the ALPPS group (P = 0.426). Overall major morbidity (Clavien-Dindo ≥ 3a) (stage 1 + stage 2) was 41.2% (n = 7) in TSH and 33.3% (n = 7) in ALPPS patients (P = 0.389), and perioperative 90-day mortalities were 11.8% (n = 2) vs. 19.0% (n = 4) in each group, respectively (P = 0.654). Intention-to-treat OS rates at 1 and 5 years in CRLM patients for TSH (n = 15) were 80% and 33%, and for ALPPS (n = 17) 76% and 35%, respectively. DFS rates at 1 and 5 years were 36% and 27% in the TSH group vs. 33% and 27% in the ALPPS group, respectively. CONCLUSIONS: ALPPS is an effective alternative to TSH in bilateral affecting liver tumors, allowing higher resection rate, but patients must be carefully selected. In CRLM patients similar long-term OS and DFS can be achieved with both techniques.

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/mm2 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.

A novel surgical technique focused on the study of the ileum: The preduodenal ileal transposition.

AIMS: Our main goal is to study the effects on the carbohydrate metabolism. Thus, we designed various experimental surgical models on healthy non-obese Wistar rats to reproduce several conditions. In this sense, we report a new experimental model. It is well known that bariatric surgery has important effects on the control of Type 2 Diabetes Mellitus. The underlying reasons are yet unknown, although the different theories focused in the release of different hormones after the pass of the nutrients through the tract. These released hormones have opposite effects that come together in a balanced glycemic metabolism. MATERIALS AND METHODS: After bariatric surgical techniques, the modified anatomy resulted in an imbalance of the secreted hormones. Wistar rats were randomized in two groups Sham and surgical group. Our model consisted on the transposition of the terminal ileum right after the pylorus. Weight gain, food intake, and basal glycemia were measured weekly. RESULTS: We did not obtain significant differences between both groups for these functional variables. CONCLUSIONS: This technique involved an early pass of the bolus through the ileum. The change on the luminal pH, along with the lack of enzymes to absorb the content, or the changes in the release of several hormones must be variables to the study. The mortality rate was assumable considering it was an experimental model on animals.

OBJETIVO: Crear un nuevo modelo quirúrgico experimental en ratas Wistar sanas no obesas para estudiar los efectos del metabolismo glucídico. Es bien sabido que las técnicas de cirugía bariátrica tienen un efecto importante sobre la resolución de la diabetes mellitus tipo 2. Se han invocado diferentes hipótesis, algunas centradas en el papel que tienen distintas hormonas secretadas por el propio tubo digestivo tras el paso de los nutrientes a su través, pero las razones últimas subyacentes permanecen desconocidas. El efecto contrapuesto de dichas hormonas consigue un efecto de control glucémico. El desequilibrio hormonal tras las alteraciones anatómicas de las cirugías bariátricas podría estar en la base de dicha mejora del metabolismo glucídico final. MATERIAL Y MÉTODOS: Las ratas fueron operadas en dos grupos (control quirúrgico y experimental) y se procedió a disponerles el íleon anastomosado al antro pilórico, previo al esfínter pilórico. Medimos distintos parámetros funcionales (ganancia de peso, ingesta y glucemias semanales). RESULTADOS: No obtuvimos diferencias significativas en la evolución de estos parámetros. CONCLUSIONES: Este modelo será útil para nuestro propósito de estudiar el íleon, en su componente secretor de enterohormonas, cuando el paso de los nutrientes se produzca tempranamente. La mortalidad fue asumible, dada la innovación técnica realizada.

Pancreas is a preeminent source of ghrelin after sleeve gastrectomy in Wistar rats.

Many surgical techniques are employed in the treatment of severe obesity. A main consequence of these techniques is the improvement of type 2 Diabetes mellitus. Ghrelin is a gut hormone released in the gastric fundus and corpus, which has been related to diabetic improvement as mentioned in these papers. Sleeve gastrectomy and Roux-en Y Gastric Bypass are surgical techniques broadly employed in humans; both severely reduce the gastric surface. Paradoxically, the serum level of ghrelin in patients is preserved. We hypothesized about the role of embryonic pancreatic epsilon cells, which have the capacity to release ghrelin. We studied the changes in the epsilon cells and differentiation markers with immunostaining and ghrelin serum level and after surgery. We employed euglycemic male Wistar rats: two surgical groups (Sleeve gastrectomy and Roux-en Y Gastric Bypass) and two control groups. We reported a significant increase of ghrelin epsilon-cells in the pancreas and basal serum after Sleeve gastrectomy versus the control groups. The epsilon cellular increment was related to neogenesis, as the neurogenin-3 marker revealed. The Roux-en Y Gastric Bypass showed neither epsilon cell increase nor basal serum changes in ghrelin release. As a conclusion, we reported that the severe suppression of the fundus gastric produced the recovery of ghrelin released by the epsilon cells, which was indicative of an ontogenic embryonic pancreatic function.

The Leading Role of Peptide Tyrosine Tyrosine in Glycemic Control After Roux-en-Y Gastric Bypass in Rats.

AIMS: Roux-en-Y gastric bypass (RYGB) is one of the most effective surgical therapies for the rapid resolution of type 2 diabetes. However, the mechanisms underlying the entero-hormonal response after surgery and the role of peptide tyrosine tyrosine (PYY) in the restoration of normoglycemia are still not clear. METHODS: We reproduced the RYGB technique in Wistar and Goto-Kakizaki rats and performed serum hormonal, histological, and hormonal-infusion test. RESULTS: Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrated that PYY plasma levels showed a remarkable peak approximately 30 min earlier than GLP-1 or GIP after mixed-meal administration in RYGB-operated rats with PYY. The GLP-1 and GIP areas under the curve (AUCs) increased after RYGB in GK rats. Additionally, the findings suggested that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Finally, the number of GLP-1-positive cells appeared to increase in the three segments of the small intestine in GK-RYGB-operated rats beyond the early presence of nutrient stimulation in the ileum. Nevertheless, PYY-positive cell numbers appeared to increase only in the ileum. CONCLUSION: At least in rats, these data demonstrate an earlier essential role for PYY in gut hormone regulation after RYGB. We understand that PYY contributes to GLP-1 and GIP release and there must be the existence of enteroendocrine communication routes between the distal and proximal small intestine.

The histomorphometric parameters of endocrine pancreas after bariatric surgery in healthy animal models.

BACKGROUND: The aim of this study is to describe in depth how different bariatric surgeries affect to the cellularity of ß-cells in the pancreatic islet. There are much data regarding the possible physiological mechanisms involved in resolution of type 2 diabetes after bariatric surgery. But these data usually are controversial. We reported a direct influence of bariatric surgical technique on endocrine pancreas cellular turnover. Some surgeries increase proliferation processes of the ß-cells. Our objective is to report the histomorphometric mechanism that these techniques stimulate over the cellularity of pancreatic islet. METHOD: To this purpose, we used adult male Wistar rats to undergo the different techniques. We developed three surgical techniques (Sleeve gastrectomy and Y-Roux Gastric bypass as the most usual bariatric techniques, and a purely malabsorptive technique); moreover two control groups were performed (Sham and fasting controls). RESULTS: We completed a sequence of morphometric studies to conclude the behaviour of endocrine pancreatic ß-cell islet, correlating several histomorphometry parameters. CONCLUSION: Our purpose was to show a comprehensive interpretation to the consequences that bariatric surgeries had on the pancreatic islets cellularity. Moreover, we included the main tests to report the cellularity in histological samples.

GLP-1 mediated improvement of the glucose tolerance in the T2DM GK rat model after massive jejunal resection.

OBJECTIVE: The aim of this study was to clarify the role of the middle gut in the entero-pancreatic axis modification that leads to glucose improvement in the Goto-Kakizaki (GK) rat as a non-obese T2DM model. BACKGROUND: Bariatric surgery is considered an assured solution for type 2 Diabetes (T2DM). Enterohormones such as ghrelin, gastric inhibitory polypeptide and mainly glucagon-like peptide-1 (GLP-1) were recognized as key players in the physiophathological mechanisms associated with entero-pancreatic axis regulation and glucose tolerance improvement. However, the influence of anatomical arrangements post-bariatric surgery on this axis is still debatable. METHOD: To this purpose, 50% of small intestine resections were performed on GK rats (n = 6), preserving the proximal half of the jejunum and the ileum (IR50). Phenotypic and functional changes, such as performance in oral glucose tolerance tests, ileal release of GLP-1, beta-cell sensitivity to GLP-1, beta-cell mass, and turnover were characterized in IR50 and the surgical control group (Sham). RESULTS: The glucose tolerance was improved and ileal release of GLP-1 was enhanced four weeks after IR50 versus the control group rats. Beta-cell mass, beta-cell proliferation, and beta-cell sensitivity to GLP-1 were also increased in the pancreas of IR50 versus the control group rats. CONCLUSION: the jejunal exclusion increases beta-cell-mass and improves glucose tolerance by increasing in GLP-1 expression and number of receptors via the entero-pancreatic axis.

The main participation of the enterohormone GLP-1 after bariatric surgery.

BACKGROUND: Numerous hypotheses are called to explain the beneficial effect on glucose metabolism after bariatric surgery. Some authors advocate for the secretion and release of various substances with endocrine functions for the explanation on this event. One of the substances most marked as effector, with contrasting effects but controversial data, is GLP-1. METHODS: Our study was performed in healthy male Wistar rats, to avoid the absence of confounding factors such as T2DM and obesity. In order to know the adaptation of GLP-1 secretion after surgery 5 groups were designated: two control groups (fasting and surgical stress), and three surgical groups (gastric sleeve, 50% resection of the midgut and the Roux en Y gastric bypass). After three months the GLP-1 synthesis in the different portions of the small intestine and the expression of the membrane receptors in pancreatic islet cells were studied by immunohistochemical techniques. RESULTS: There was a significant increase in the number of secretory cells in ileum, duodenum and jejunum in mixed (RYGB) and malabsorptive (RI50) surgical groups. An elevation of pancreatic receptors signal was also observed in the same techniques versus controls. CONCLUSIONS: Our data indicate that intestinal secretion of GLP-1 and its sensitivity to the pancreatic changes were increased like a response of an adaptive effect to the mechanical aggression of the digestive tube and as alteration of nutrient flow after surgery.

La controvertida participación del GLP-1 en los mecanismos fisiológicos desencadenados tras cirugía bariátrica / The controversial participation of GLP-1 in the physiological mechanisms unchained after bariatric surgery

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.

SUMMARY: Numerous hypotheses are invoked to explain the beneficial effect on glucose metabolism after bariatric surgery. Some authors advocate for the secretion and release of various substances with endocrine functions (enterohormones). One of the substances most marked as effector, with contrasting effects but controversial data, is Glucagon-like peptide-1 GLP-1. Our study was performed in healthy male Wistar rats, to avoid the absence of confounding factors such as DMT2 and obesity. In order to know the map of adaptation to GLP-1 secretion after surgery, five groups were designated: Two control groups (fasting and surgical stress); and three surgical groups (vertical sleeve gastrectomy, 50 % midgut resection and Roux-en-Y gastric bypass). After three months, the GLP-1 synthesis pattern was studied by immunohistochemical techniques in the different portions of the small digestive tract. The expression of membrane receptors in pancreatic islet cells was also studied. There was a significant increase in the number of secretory cells in ileum, duodenum and jejunum in mixed surgical (RYGB) and malabsorptive (RI50) groups. An elevation of pancreatic receptors was also observed in the same techniques against controls. Our data indicated that intestinal secretion of GLP1 and its sensitivity to the pancreatic level were increased, both to an adaptive effect to the mechanical aggression of the digestive tube and to the alteration of nutrient flow after surgery.

Bariatric surgery influences ß-cell turnover in non obese rats.

BACKGROUND: The aim of this study was to investigate the relation between the different bariatric surgeries and pancreatic ß-cell turnover. MATERIAL AND METHODS: We used healthy adult male Wistar rats to undergo the different techniques. Three surgical techniques were developed (malabsorptive, Sleeve gastrectomy and Roux-Y Gastric Bypass-), together with two control groups (Sham and fasting control). Pancreatic ß-cell mass was measured, as well as apoptosis, proliferation and neogenesis related to cellular turnover. Otherwise, we measured the functional issues to elucidate the physiological role that these surgical techniques trigger in the carbohydrate metabolism (e.g. food intake, weight gain, intraperitoneal glucose tolerance test, and basal glycaemia). Results included the differences in phenotypes of the rat after the surgery. The rats did not show important differences in glycaemic parameters between the surgical groups. The ß-cell mass presented modifications related with proliferation processes. A significant increase of ß-cell mass in the malabsorptive technique was reported. On the other hand, the peripheral resistance to insulin tended to be reduced in rats which underwent malabsorptive and mixed techniques. CONCLUSION: This work showed an increase in ß-cell mass after the resection of an important portion of small bowel. The Roux-Y Gastric Bypass produced a non-significant increase in ß-cell mass. We considered that these implications of surgery over the endocrine pancreas must be one of the mechanisms related to the improvement of type 2 Diabetes mellitus following bariatric surgery.