Banca de DEFESA: ISAIANE MEDEIROS

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : ISAIANE MEDEIROS
DATE: 27/12/2024
TIME: 14:00
LOCAL: Sala de reuniões do Departamento de Nutrição (DNUT) e https://meet.google.com/vgd-wqrn-hbe
TITLE:

STUDY OF THE EFFECT OF NATURAL BIOACTIVE PROTEINS AND PEPTIDES IN THE TREATMENT OF DIABETES MELLITUS

KEY WORDS:

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

PAGES: 100
BIG AREA: Ciências Biológicas
AREA: Bioquímica
SUMMARY:

Diabetes mellitus (DM) is a public health problem characterized by hyperglycemia. The aim of this study was to evaluate the effect of natural bioactive proteins and peptides in the treatment of DM. Thus, this thesis is divided into three chapters. The first chapter describes the protocol for the systematic review (SR), which was registered in the International Register of Prospective Systematic Reviews (PROSPERO, number: CRD42022355540) and guided the construction of the SR presented in the second chapter. In the second chapter, the SR was conducted with the objective of answering the starting question: which peptides or proteins have been studied in silico for the treatment of diabetes mellitus? The articles were selected based on PECOs (Population, Exposure, and Context) from the databases PubMed, ScienceDirect, Scopus, Web of Science, Virtual Health Library, and EMBASE. Based on eligibility criteria, 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 extracted from natural sources interacted in silico with therapeutic targets involved in DM management, such as α-amylase, dipeptidyl peptidase IV (DPP-IV), α-glucosidase, insulin receptor (IR), glucose transporter type 2 (GLUT-2), and sodium-glucose co-transporter protein (SGLT1). When re-evaluated in vivo, these interactions promoted a reduction in fasting blood glucose, improvement in pancreatic morphology, positive regulation of insulin secretion and expression, reduction or maintenance of plasma insulin levels, a decrease in HOMA-IR, an increase in HOMA-β, and maintenance of GLP-1. This demonstrated that in silico studies provided crucial insights into therapeutic strategies for DM. In the third chapter, a preclinical study was conducted to evaluate the effect of trypsin inhibitor isolated from tamarind seed (ITT) in zebra fish with increased fasting blood glucose developed by overfeeding with Artemia sp., aiming to determine the mechanism of action of this inhibitor through glycation or insulin-like pathways. Biochemical parameters, relative expression of the IR gene, and morphological changes in organs and tissues relevant to type 2 diabetes (T2DM) and protein glycation (in vitro and in vivo) were evaluated. The diagnosis of T2DM was made using Accu-Chek® for fasting blood glucose measurement before treatment began. The animals (n = 140), of both sexes, were divided into four groups (n = 35): 1) healthy, untreated, and normo-fed animals, 2) T2DM animals without treatment and overfed, 3) T2DM animals treated with 25 mg of ITT/L and overfed, and 4) T2DM animals 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 pre-treatment (p = 0.008). After treatment, a significant reduction (p < 0.01) in fasting blood glucose, HOMA-IR, and QUICKI index, and a significant increase (p < 0.01) in HOMA-β were observed in the animals treated with ITT and overfeeding compared to the untreated T2DM group. However, these values showed no significant difference (p > 0.05) compared to the healthy animals, except for the QUICKI index. A significant increase (p < 0.01) in insulin was observed in all groups compared to the healthy control. 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/mL, while the concentration of 25 mg/mL of ITT significantly increased (p < 0.01). This finding did not persist when checking the formation of advanced glycation end products (AGEs) in vivo (p > 0.05) among the groups treated with 25 mg of ITT/L. Additionally, ITT promoted negative regulation of relative IR expression in adipose tissue and skeletal muscle. Histopathological findings showed reduced visceral adiposity, pancreatic and hepatic steatosis, and renal degeneration in animals treated with ITT and overfeeding. However, further studies are still needed to elucidate the mechanisms of fasting blood glucose reduction.

COMMITTEE MEMBERS:
Externa ao Programa - 2323511 - ADRIANA AUGUSTO DE REZENDE - nullPresidente - 2578619 - ANA HELONEIDA DE ARAUJO MORAIS
Externa à Instituição - ANA LUISA PIRES MOREIRA - UFPB
Externo à Instituição - AUGUSTO MONTEIRO DE SOUZA
Externo à Instituição - EDUARDO BORGES DE MELO - UNIOESTE