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.

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.

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.

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.