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Effects of ileal transposition on the endocrine pancreas of normal rats

Grant number: 11/23086-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): April 01, 2012
Effective date (End): March 31, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Joao Luiz Moreira Coutinho de Azevedo
Grantee:Rodrigo Yuzo Masuda
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Obesity presents itself as a global epidemic, because of its increasing incidence and prevalence, with important implications biopsychosocial and large financial impact on the world economy. According to the World Health Organization, in 2005, there were approximately 400 million obese people worldwide and 1.6 billion overweight. In Brazil, according to the Consumer Expenditure Survey (POF 2002-2003) of the Brazilian Institute of Geography and Statistics estimated that about 50% of the population is above the ideal weight. Insulin resistance and diabetes mellitus (DM) are conditions that are related to obesity, but the pandemic of type 2 diabetes affects not only obese, but also people with Body Mass Index (BMI) below. There is an increasing prevalence and an incidence of type 2 diabetes in individuals with a BMI in the overweight and normal weight range. Thus, identification of hormones released by cells of the digestive tract has assumed an important role in understanding the relationship between these hormones and carbohydrate metabolism. The production of the hormone glucagon similar to type 1 (Glucagon-like peptide type 1: GLP-1) is performed in L cells, found mainly in the ileum and proximal colon, and part of the enterohepatic endocrine and producing various hormones from the cleavage of a macromolecule, the pro-glucagon.The main actions of GLP-1 are: stimulation of the synthesis of insulin by the beta cells of pancreatic islets, reduced peripheral insulin resistance and consequent effect on glucose metabolism. This has demonstrated its effect in stimulating the production of insulin, implying the possibility of treatment of type 2 diabetes. Regarding the endocrine pancreas, recent studies have shown that GLP-1 increases beta cell proliferation and inhibits apoptosis of these, stimulating the growth of pancreatic islets. In addition, at the molecular level, it was found that GLP-1 acts on the differentiation of primitive cells in the pancreas beta cells. Idealized for the purpose of weight reduction, several surgical techniques have been effective in the treatment of metabolic syndrome, particularly type 2 diabetes. Studies have shown that most obese or diabetic patients who underwent surgical treatment showed improvement of DM before a significant weight loss. The hypothesis for this is that changes in the anatomical configuration of the digestive tract, as determined by surgical intervention, cause the release of incretin hormones, ie, act in the production of endocrine hormones enterohepatic in cell sensitivity to insulin and metabolism of carbohydrates. Some bariatric surgical procedures shorten the route to the terminal ileum, allowing fully digested foods do not reach the distal small intestine, stimulating the release of GLP-1 by enterohepatic endocrine cells of the type L, the existing high density distal ileum. This is what happens when transported surgically segment of terminal ileum and interpose in the proximal jejunum. Another effect of this increase in blood levels of GLP-1 is the decrease in motility of the digestive tract, terming this intervention "ileal brake". Therefore, the aim of the project is to evaluate the effects on the endocrine pancreas of a surgical technique designed to interfere with the enterohepatic endocrine function of the host by checking the histological and morphological changes occurring in the pancreatic islets after ileal interposition.Histological evaluation will be performed by immunohistochemistry. Expected to be observed in the group undergoing ileal transposition: lower feed intake, reduced weight gain, increase in the number of beta cells in islets, histological signs of beta-cell hyperactivity and hypoactivity of alpha cells, evaluating the effectiveness of this surgical technique through the incretin effect of GLP-1 acting in the endocrine pancreas.