BIOACTIVE VEGETABLE PROTEINS AND THEIR EFFECTS ON GLYCEMIC CONTROL
Hypoglycemic agents. Plant proteins. Signal transduction. Diabetes therapy. Vegetable proteins
Type 2 diabetes mellitus (DM2) is a global public health problem. Therefore, this thesis aims to analyze the effect of plant-based bioactive proteins on blood glucose control. The thesis was divided into three chapters, in the first and second the protocol and the systematic review (SR) were presented, aiming to answer the following question: how proteins and isolated and purified peptides extracted from vegetables act in the reduction of blood glucose in experimental models of DM2? The protocol was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) under the number: CRD42019110956. For RS, experimental studies were selected with bioactive proteins and peptides of plant origin with an effect on DM2. The articles were selected according to eligibility criteria according to PICOS (population, interventions, control, results and type of study) in the databases: PubMed, ScienceDirect, Scopus, Web of Science, EMBASE and Virtual Health Library (VHL) , in March 2019. The initial search retrieved 916 articles and, after reading the title, abstract and keywords, 24 articles were eligible for full reading. After that, five articles were included in the RS. The assessment of evidence and strength of study recommendations was performed using the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) protocol. As a result of RS, it was seen that all pathways stimulated by the five bioactive molecules of protein origin mediated secondary stimuli in the insulin signaling cascade up to glucose uptake. The third chapter presents the study with the isolated tamarind trypsin inhibitor (ITT) and ITTp number 56, and conformation number 287 (ITTp 56/287). In the preclinical study, the effect of ITT on the hyperglycemic state in Wistar rats with DM2 induced by a high glycemic index and high glycemic load (HGLI) diet for 17 weeks was evaluated. From the diagnosis of DM2 the animals (n = 15) were divided into three groups (n = 5): 1. DM2 without treatment, 2. DM2 treated with standard diet (nutritionally adequate) and 3. DM2 treated with ITT (25 mg/kg), administered by 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 for β-cell function (HOMA-β). It was observed that the group of animals that received the treatment with the ITT presented a significant reduction in fasting glucose (p = 0.0031) and in the HOMA-IR index (p = 0.0432), in addition to an increase in the HOMA- β (p = 0.0052) when compared to the other evaluated groups. In the study by molecular dynamics simulation (DM), still in progress, it was possible to observe, through molecular docking, an interaction between the ITTp 56/287 and the insulin receptor (IR) (PDB ID 4OGA). Thus, it appears that vegetable proteins, such as ITT, have antidiabetic potential as an adjuvant in hyperglycemic control through acting in metabolic pathways common to IR.