Banca de QUALIFICAÇÃO: ISAIANE MEDEIROS

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
STUDENT : ISAIANE MEDEIROS
DATE: 26/09/2024
TIME: 14:00
LOCAL: Sala de reuniões do Departamento de Nutrição, UFRN
TITLE:

EFFECT OF PROTEINS AND PEPTIDES IN THE TREATMENT OF DIABETES MELLITUS

KEY WORDS:

Tamarindus indica L. Hyperglycemia. Computer simulation. Systematic review. Danio rerio.

PAGES: 77
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Diabetes mellitus (DM) is a public health issue characterized by hyperglycemia. The aim of this study was to evaluate the effect of proteins and peptides in the treatment of DM. This thesis is divided into three chapters. The first chapter details the protocol for the systematic review (SR), which was registered with the International Register of Prospective Systematic Reviews (PROSPERO) and guided the construction of the SR presented in the second chapter. The goal was to answer the initial research question: which peptides or proteins have been studied in silico for the treatment of diabetes mellitus? Articles were selected based on PECOs (Population, Exposure, and Context) from the databases PubMed, ScienceDirect, Scopus, Web of Science, Virtual Health Library, and EMBASE. Five articles were included, and the risk of bias was assessed using the adapted Strengthening the Reporting of Empirical Simulation Studies (STRESS) tool. The results showed that proteins and/or peptides derived from natural sources bind in silico to therapeutic targets such as α-amylase, dipeptidyl peptidase IV (DPP-IV), α-glucosidase, insulin receptor (IR), glucose transporter type 2 (GLUT-2), and sodium-glucose transport protein (SGLT1), and in vivo, they demonstrate reduced fasting blood glucose, improved pancreatic morphology, positive regulation of insulin secretion and expression, reduced or maintained plasma insulin, decreased HOMA-IR, increased HOMA-β, and maintenance of GLP-1. In the third chapter, a preclinical study was conducted to evaluate the effect of tamarind seed trypsin inhibitor (ITT) in a zebrafish model with diet-induced DM, in order to elucidate the mechanism of action of this inhibitor via glycation and insulin-like pathways. DM diagnosis was made using Accu-Chek® for fasting blood glucose measurement before the start of treatments. The animals (n = 140) were divided into four groups (n = 35): 1) healthy animals without treatment and normo-fed, 2) animals with DM without treatment and overfed, 3) animals with DM treated with 25 mg of ITT/L and overfed, and 4) animals with DM treated with 25 mg of ITT/L and normo-fed for 10 days. Fasting blood glucose was 62.33 mg/dL (2.52) for normo-fed animals and 104.70 mg/dL (4.16) for overfed animals before treatment (p = 0.008). After treatment, there was a significant reduction (p < 0.01) in fasting blood glucose and HOMA-IR, and a significant increase (p < 0.01) in HOMA-β in animals treated with ITT and overfed compared to the DM2 control group, although these values did not show a significant difference (p > 0.05) from the healthy controls. Meanwhile, there were significant increases and decreases (p < 0.01) in insulin and QUICKI index, respectively, in untreated and treated DM2 animals compared to healthy controls. No significant change (p > 0.05) in in vitro glycation of bovine serum albumin was observed for ITT concentrations of 1.4 and 5 mg, whereas the 25 mg concentration of ITT significantly increased (p < 0.01). This finding was not maintained when assessing AGE formation in vivo (p > 0.05) among the analyzed groups. It is suggested that ITT acts in an insulin-like manner as demonstrated by the positive regulation (p > 0.05) of IR expression and does not act via protein glycation. Thus, further studies are needed to fully elucidate this signaling pathway.

COMMITTEE MEMBERS:
Externa ao Programa - 2323511 - ADRIANA AUGUSTO DE REZENDE - nullPresidente - 1549705 - ADRIANA FERREIRA UCHOA
Externa ao Programa - 2275877 - THAIS SOUZA PASSOS - null