Organic consequences of ileal transposition in rats with diet-induced obesity

INTRODUCTION: The clinical management of metabolic syndrome - especially diabetes mellitus type 2 - is notoriously complex due to the progressive nature of this disease. At present, there is a need for a surgical procedure that is effective for the treatment of diabetes mellitus type 2, even in non-obese individuals. The isolated ileal transposition theory could lead to an effective alternative therapy. This intervention has not yet been performed in humans, and there are no reports of its use in an experimental model of diet-induced metabolic syndrome.
 OBJECTIVES: The objective of this study is to evaluate the physiological effects of ileal transposition in rats with diet-induced metabolic syndrome. The effects of this procedure on glucose and lipid metabolism will be assessed. 
METHODS: Forty 12-week-old male rats (albino Rattus norvegicus, Wistar, 2BAW, heterogeneous) will be divided into four groups of 10 animals each: the ileal transposition group (TG) comprising animals on a hypercaloric-hyperlipidic diet; the sham group (SG) containing animals that receive the same diet and undergo the sham surgery; control group 1 (CG1), which will receive a hypercaloric-hyperlipidic diet and will not undergo surgery; and control group 2 (CG2), which will consume standard feed and will not undergo surgery. The surgeries will be performed in 20-week-old animals. Blood samples for laboratory testing will be collected from 12-week-old animals on the day of surgery and after eight postoperative weeks, following determination of the weights of the animals and the administration of anesthesia. The levels of serum glucose, insulin, triglycerides, total cholesterol and fractions, glucagon-like peptide-1, C-peptide and glycated hemoglobin will be assessed in all of the animals. The insulin tolerance test will be performed using PRISMA software, and insulin resistance will be calculated by the HOMA-IR indirect test. On specific days, two 20-week-old rats will be separated and randomly distributed in TG and SG. These animals will be followed until the eighth postoperative week. Subsequently, they will be euthanized, and the retroperitoneal and periepididymal fat deposits will be collected and weighed using a precision scale. In addition, the pancreas, liver and intestinal segments will be sent for pathological and immunohistochemical studies.
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Isolated ileal interposition in enteroendocrine L cells differentiation

INTRODUCTION: 
Due to the progressive nature of type 2 diabetes, its complexity and drug treatment perpetuity, there is currently a search for surgical procedures that can promote euglycemia also in non-obese patients. Diabetic patients glycemic control can be achieved by increasing the blood concentration of GLP-1, a hormone produced by L cells that are more densely concentrated in the terminal ileum. Early and extended improvement of diabetes in patients submitted to bariatric surgeries awakened the necessity of investigating the isolated ileal interposition as a surgical alternative for the treatment of diabetes. The interposition of this ileal segment to a more anterior region (proximal jejunum) can promote a greater stimulation of the L cells by poorly digested food, increasing the production of GLP-1 and reflecting on glycemic control. However, in order to consolidate the ileal interposition as a surgical treatment of diabetes it is necessary that the interposed ileum keep the same differentiation rate into L cells for a long period to justify the intervention.

AIMS: 
To investigate the isolated ileal interposition influence on the differentiation of intestinal precursor cells into enteroendocrine L cells over time.

METHODS: 
Twelve 12-week-old male Wistar rats (Rattus norvegicus albinus) of the WAB strain (heterogeneous) will be used. All animals will receive a high-calorie, high-fat diet for 16 weeks or more until they develop glucose dysmetabolism confirmed by glycemic test. They will be divided into two groups of 10 animals each: the isolated ileal interposition group (GI) and the control group (GC), comprising animals that will not be submitted to any surgical intervention. Blood samples will be collected under anesthesia at the weeks 12, 26, 36 and 44 for the determination of serum levels of glucose, insulin, GLP-1, glucagon, C-peptide and glycosilated hemoglobin. The insulin tolerance test will be performed and insulin resistance will be calculated. For the comparative analysis of the ileal precursor cells differentiation into enteroendocrine cells among the two groups, the following intestinal fragments will be collected after euthanasia: interposed ileum and remaining ileum from GI, jejunum and ileum from GC. These fragments will be analyzed by imunofluorescence and also by Real Time PCR using PCR Arrays for target genes including the main ones related to stem cell, stem cell signaling, diabetes, Wnt and Notch signaling pathways and other genes and pathways involved in the differentiation of intestinal precursor cells into enteroendocrine cells, especially GLP-1-producing L cells that play important role in euglycemia