Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico
Type 2 diabetes mellitus (T2DM) is a disease characterized by a chronic state of hyperglycemia, which can trigger changes in the body's functional and structural properties. Thus, the objective was to analyze the mechanism of action and the effect of bioactive proteins of plant origin in contro...
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Diabetes mellitus tipo 2 Agentes hipoglicemiantes Proteínas vegetais Tamarindus indica L. Simulação de dinâmica molecular |
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Diabetes mellitus tipo 2 Agentes hipoglicemiantes Proteínas vegetais Tamarindus indica L. Simulação de dinâmica molecular Costa, Izael de Sousa Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico |
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Type 2 diabetes mellitus (T2DM) is a disease characterized by a chronic state of
hyperglycemia, which can trigger changes in the body's functional and structural
properties. Thus, the objective was to analyze the mechanism of action and the effect of
bioactive proteins of plant origin in controlling blood glucose in the context of T2DM,
seeking new therapeutic targets for this disease. This thesis was divided into three
chapters. In the first and second, there are the protocol and the systematic review (SR),
respectively, aiming to answer the question: how the isolated (pool) and purified
proteins and peptides extracted from vegetables act to reduce blood glucose in
experimental models of T2DM? The protocol was registered in the International
Prospective Registry of Systematic Reviews (PROSPERO) under CRD42019110956.
For SR, experimental studies were selected with bioactive proteins and peptides of plant
origin that affect the glycemic control of animals with experimentally induced T2DM.
The articles were selected according to the PICOS strategy (population, interventions,
control and outcome) in the following databases: PubMed, ScienceDirect, Scopus, Web
of Science, EMBASE and Virtual Health Library. The initial search retrieved 916
articles. After reading the title, abstract and keywords, 24 articles were eligible for a full
reading. After this process, five articles were included in the SR. The study's assessment
of evidence and risk of bias was performed using the Systematic Review Center for
Laboratory Animal Experimentation (SYRCLE) protocol. As a result of the SR, all
pathways stimulated by the five molecules of vegetable protein origin mediated
secondary stimuli in the insulin signaling cascade up to glucose uptake. In the third
chapter, a preclinical study with the trypsin inhibitor isolated from tamarind seed (TTI)
and in silico analysis with the TTIp model number 56 and conformation number 287
(TTIp 56/287) was presented. In the preclinical study, the effect of TTI on the
hyperglycemic state in Wistar rats with T2DM induced by a high glycemic index and
high glycemic load (HGLI) diet for 17 weeks was evaluated. From the diagnosis of
T2DM, the animals (n = 15) were divided into three groups (n = 5): 1. T2DM without
treatment; 2. T2DM treated with a standard diet (nutritionally adequate); and 3. T2DM
treated with TTI (25 mg/kg), administered by oral gavage (1 ml) for 10 days. After this
period, fasting insulin and glycemia were analyzed, in addition to the Homeostasis
model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β)
models. At the end of the analysis, the group of animals that received the treatment with
the TTI had lower fasting glucose concentration (p = 0.0031) and the HOMA-IR index
(p = 0.0432), in addition to being higher HOMA-β index (p = 0.0052) when compared
to the animals of the other groups evaluated. In the study by molecular dynamics
simulation, the interaction between the TTIp 56/287 and the insulin receptor (IR) (PDB
ID 4OGA) was observed. The TTIp 56/287-IR (-1591.54 kJ mol-1 ± 234.90), showed
lower potential energy of interaction (EPI) compared to the Insulin-IR (Ins-IR) (-894.98
kJ mol-1 ± 32.16), with distinct amino acid residues involved in this interaction. Thus, TTI acted as a hypoglycemic agent in a preclinical study, and its connection to RI can
trigger this action. This thesis shows that plant proteins, such as TTI, have antidiabetic
potential as an adjuvant in glycemic control by acting in metabolic pathways common to RI. |
| author2 |
Morais, Ana Heloneida de Araújo |
| author_facet |
Morais, Ana Heloneida de Araújo Costa, Izael de Sousa |
| format |
doctoralThesis |
| author |
Costa, Izael de Sousa |
| author_sort |
Costa, Izael de Sousa |
| title |
Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico |
| title_short |
Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico |
| title_full |
Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico |
| title_fullStr |
Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico |
| title_full_unstemmed |
Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico |
| title_sort |
proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico |
| publisher |
Universidade Federal do Rio Grande do Norte |
| publishDate |
2021 |
| url |
https://repositorio.ufrn.br/handle/123456789/45474 |
| work_keys_str_mv |
AT costaizaeldesousa proteinasepeptideosbioativosdevegetaiseseusmecanismosenvolvidosnocontroleglicemico AT costaizaeldesousa bioactivevegetableproteinsandpeptidesandtheirmechanismsinvolvedinglycemiccontrol |
| _version_ |
1773957573186158592 |
| spelling |
ri-123456789-454742022-05-02T15:08:12Z Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico Bioactive vegetable proteins and peptides and their mechanisms involved in glycemic control Costa, Izael de Sousa Morais, Ana Heloneida de Araújo http://lattes.cnpq.br/2516503036471108 http://lattes.cnpq.br/1233944493334651 Monteiro, Norberto de Kassio Vieira 05011738469 http://lattes.cnpq.br/8804303821523487 Rezende, Adriana Augusto de http://lattes.cnpq.br/4245215108740331 Marinho, Emmanuel Silva http://lattes.cnpq.br/3617101885685308 Aquino, Jailane de Souza http://lattes.cnpq.br/8153908179932184 Evangelista, Karine Cavalcanti Mauricio de Sena http://lattes.cnpq.br/2628723272728505 Diabetes mellitus tipo 2 Agentes hipoglicemiantes Proteínas vegetais Tamarindus indica L. Simulação de dinâmica molecular Type 2 diabetes mellitus (T2DM) is a disease characterized by a chronic state of hyperglycemia, which can trigger changes in the body's functional and structural properties. Thus, the objective was to analyze the mechanism of action and the effect of bioactive proteins of plant origin in controlling blood glucose in the context of T2DM, seeking new therapeutic targets for this disease. This thesis was divided into three chapters. In the first and second, there are the protocol and the systematic review (SR), respectively, aiming to answer the question: how the isolated (pool) and purified proteins and peptides extracted from vegetables act to reduce blood glucose in experimental models of T2DM? The protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) under CRD42019110956. For SR, experimental studies were selected with bioactive proteins and peptides of plant origin that affect the glycemic control of animals with experimentally induced T2DM. The articles were selected according to the PICOS strategy (population, interventions, control and outcome) in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, EMBASE and Virtual Health Library. The initial search retrieved 916 articles. After reading the title, abstract and keywords, 24 articles were eligible for a full reading. After this process, five articles were included in the SR. The study's assessment of evidence and risk of bias was performed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) protocol. As a result of the SR, all pathways stimulated by the five molecules of vegetable protein origin mediated secondary stimuli in the insulin signaling cascade up to glucose uptake. In the third chapter, a preclinical study with the trypsin inhibitor isolated from tamarind seed (TTI) and in silico analysis with the TTIp model number 56 and conformation number 287 (TTIp 56/287) was presented. In the preclinical study, the effect of TTI on the hyperglycemic state in Wistar rats with T2DM induced by a high glycemic index and high glycemic load (HGLI) diet for 17 weeks was evaluated. From the diagnosis of T2DM, the animals (n = 15) were divided into three groups (n = 5): 1. T2DM without treatment; 2. T2DM treated with a standard diet (nutritionally adequate); and 3. T2DM treated with TTI (25 mg/kg), administered by oral gavage (1 ml) for 10 days. After this period, fasting insulin and glycemia were analyzed, in addition to the Homeostasis model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) models. At the end of the analysis, the group of animals that received the treatment with the TTI had lower fasting glucose concentration (p = 0.0031) and the HOMA-IR index (p = 0.0432), in addition to being higher HOMA-β index (p = 0.0052) when compared to the animals of the other groups evaluated. In the study by molecular dynamics simulation, the interaction between the TTIp 56/287 and the insulin receptor (IR) (PDB ID 4OGA) was observed. The TTIp 56/287-IR (-1591.54 kJ mol-1 ± 234.90), showed lower potential energy of interaction (EPI) compared to the Insulin-IR (Ins-IR) (-894.98 kJ mol-1 ± 32.16), with distinct amino acid residues involved in this interaction. Thus, TTI acted as a hypoglycemic agent in a preclinical study, and its connection to RI can trigger this action. This thesis shows that plant proteins, such as TTI, have antidiabetic potential as an adjuvant in glycemic control by acting in metabolic pathways common to RI. Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq O diabetes mellitus tipo 2 (DM2) é uma doença caracterizada pelo estado de hiperglicemia crônico, que pode desencadear alterações das propriedades funcionais e estruturais do organismo. Sendo assim, objetivou-se analisar o mecanismo de ação e o efeito de proteínas bioativas de origem vegetal no controle da glicemia no contexto do DM2, e com isso, buscar novos alvos terapêuticos para essa doença. Esta tese foi dividida em três capítulos, no primeiro e segundo tem-se o protocolo e a revisão sistemática (RS), respectivamente, visando responder à pergunta: como as proteínas e peptídeos isolados (pool) e purificados extraídos de vegetais atuam na redução da glicose sanguínea em modelos experimentais de DM2? O protocolo foi registrado no registro prospectivo internacional de revisões sistemáticas (PROSPERO) sob o número: CRD42019110956. Para a RS, foram selecionados estudos experimentais com proteínas e peptídeos bioativos de origem vegetal com efeito sobre o controle glicêmico de animais com DM2 induzido experimentalmente. Os artigos foram selecionados de acordo com a estratégia PICOS (população, intervenções, controle e desfecho) nas bases de dados: PubMed, ScienceDirect, Scopus, Web of Science, EMBASE e Biblioteca Virtual em Saúde. A busca inicial recuperou 916 artigos e, após a leitura de título, resumo e palavras-chave, 24 artigos foram elegíveis para leitura completa. Após esse processo, cinco artigos foram incluídos na RS. A avaliação das evidências e do risco de viés dos estudos foi realizada, utilizando o protocolo Systematic Review Center for Laboratory animal Experimentation (SYRCLE). Como resultados da RS foi constatado que, todas as vias estimuladas pelas cinco moléculas de origem proteica de vegetais, mediaram estímulos secundários na cascata de sinalização da insulina até a captação da glicose. No terceiro capítulo, foi apresentado um estudo pré-clínico com o inibidor de tripsina isolado de semente de tamarindo (ITT), e análises in sílico com o ITTp modelo número 56, e conformação número 287 (ITTp 56/287). No estudo pré-clínico foi avaliado o efeito do ITT sobre o estado hiperglicêmico em ratos Wistar com DM2 induzido por dieta de alto índice glicêmico e alta carga glicêmica (HGLI) por 17 semanas. A partir do diagnóstico do DM2 os animais (n = 15) foram divididos em três grupos (n = 5): 1. DM2 sem tratamento; 2. DM2 tratado com dieta padrão (nutricionalmente adequada); e 3. DM2 tratado com ITT (25 mg/kg), administrados por gavagem oral (1 mL) por 10 dias. Após esse período, foi analisada a insulinemia e glicemia de jejum, além dos modelos de Homeostasis model assessment for insulin resistance (HOMA-IR) e do for β-cell function (HOMA-β). Ao final das análises foi observado que o grupo de animais que receberam o tratamento com o ITT, apresentaram menor concentração de glicose de jejum (p = 0,0031) e do índice HOMA-IR (p = 0,0432), além de maior índice HOMA-β (p = 0,0052) quando comparado aos animais dos demais grupos avaliados. No estudo por simulação de dinâmica molecular foi possível observar interação entre o ITTp 56/287 e o receptor de insulina (RI) (PDB ID 4OGA), o ITTp 56/287-RI (-1591,54 kJ mol-1 ± 234,90) apresentou menor energia potencial de interação (EPI) comparado a Insulina-RI (Ins-RI) (-894,98 kJ mol-1 ± 32,16), com resíduos de aminoácidos distintos envolvidos nessa interação. Sendo assim, foi possível identificar que o ITT atuou como agente hipoglicemiante em estudo préclínico, e estsa ação pode ser desencadeada pela sua ligação ao RI em estudo de simulação computacional. Com esta tese, pode-se constatar que proteínas vegetais, como o ITT, tem potencial antidiabético como adjuvante no controle glicêmico por meio de atuação em vias metabólicas comuns ao RI. 2021-12-17T23:07:04Z 2021-12-17T23:07:04Z 2021-09-24 doctoralThesis COSTA, Izael de Sousa. Proteínas e peptídeos bioativos de vegetais e seus mecanismos envolvidos no controle glicêmico. 2021. 94f. Tese (Doutorado em Bioquímica e Biologia Molecular) - Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal, 2021. https://repositorio.ufrn.br/handle/123456789/45474 pt_BR Acesso Aberto application/pdf Universidade Federal do Rio Grande do Norte Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM BIOQUÍMICA |