L-Cell Activity in Small Intestine as Biliopancreatic Loop in Obese Patients With DM2 Submitted to RYGBP

Description

This is a prospective, randomized (paired) and morphological study involving 20 adult male and female patients (18-65 years) with severe obesity [body mass index (BMI) > 35 kg/m2] and DM2 undergoing Gastroplasty in Diversion Roux-en-Y in the Bariatric and Metabolic Surgery Unit, Department of Gastroenterology, HC-FMUSP, between February 2020 and December 2022. Patients were randomized (https://hcbredcap.com.br/) into two groups of 10 patients each, according to the extension of the bilio-pancreatic loop, in a proportion of 1:1 by computer model. Patients were evaluated preoperatively (T0) and 6 months (T1) after GDYR.

INTRODUTION: Patients with obesity have a suppressed incretin effect and a consequent imbalance of glycemic homeostasis. Bariatric surgery has the potential of T2DM control in up to 90% of patients with severe obesity due to caloric restriction, improvement of insulin resistance, pancreatic beta cell function, and the incretin effect of glycogen-like protein 1.

In this current scenario, metabolic surgery has taken a considerable role in weight loss, contributing to metabolic control, and showing improvement in the state of obesity and related comorbidities. We already know that conservative treatment has been failing 80% of obese patients, while 80% of obese patients who have undergone metabolic surgery are successful in long-term weight loss and resumption of metabolic functionality, showing better results than drug therapy or only lifestyle change 16 . This adaptive procedure, which is aimed at neuroendocrine improvements instead of gastrointestinal restriction and malabsorption 24 , leads to increased serum levels of the incretins (hormones that stimulate a decrease in blood glucose levels) glucagon- like peptide-1 (GLP-1) and peptide YY (PYY 3-36 ) in postprandial patients five years following surgery. They play key roles in stimulating the secretion of insulin by the endocrine pancreas . It is therefore of considerable importance to understand the secretion mechanisms of epithelial intestinal cells as well as the identity and location of cells responsible for the action of these peptides . In the intestinal epithelium we find cells that release incretins to the response of nutrients in contact with intestinal lumen called L cells . L cell found in the distal ileum and large intestine secretes GLP-1 and peptide YY (PYY) promotes they slow gastric emptying and act as a satiety signal to improve glycemic control.

JUSTIFICATION: number of L cells in activity implies better peptide signaling, response and functioning of the neuroendocrine system.

OBJECTIVE: To analize secretion of L cells in the small intestine for immunohistochemistry and mRNA expression levels before and after (6 months) induced by bariatric surgery .

METHODS: Ethic This study was elaborated and will be performed at the Clinical Hospital of the Medical School of the University of São Paulo (HCFMUSP). The patients involved will receive the Informed Consent Form (ICF) for their agreement to participate in the study.

The molecular markers(qRT-PCR) used will be the expression enterohormones themselves by the L cell, that is, GLP-1 and PYY.

The detection of incretin by Immunohistochemical assays, will enable cell labeling and localization, and evidence of cell occurrence/density in portions of the gastrointestinal tract.

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