An Insulin Receptor-Binding Multifunctional Protein from Tamarindus indica L. Presents a Hypoglycemic Effect in a Diet-Induced Type 2 Diabetes—Preclinical Study
Izael de Sousa Costa, Mayara Santa Rosa Lima, Amanda Fernandes de Medeiros, Lucas Lima Bezerra, Paula Ivani Medeiros dos Santos, Alexandre Coelho Serquiz, Maíra de Castro Lima, Gerciane Silva de Oliveira, Elizeu Antunes dos Santos, Bruna Leal Lima Maciel, Norberto de Kássio Vieira Monteiro, Ana Heloneida de Araújo Morais
Abstract
The objectives of this study were to evaluate the hypoglycemic effect of the trypsin inhibitor isolated from tamarind seeds (TTI) in an experimental model of T2DM and the in silico interaction between the conformational models of TTI 56/287 and the insulin receptor (IR). After inducing T2DM, 15 male Wistar rats were randomly allocated in three groups (n = 5): 1—T2DM group without treatment; 2—T2DM group treated with adequate diet; and 3—T2DM treated with TTI (25 mg/kg), for 10 days. Insulinemia and fasting glucose were analyzed, and the HOMA-IR and HOMA-β were calculated. The group of animals treated with TTI presented both lower fasting glucose concentrations (p = 0.0031) and lower HOMA-IR indexes (p = 0.0432), along with higher HOMA-β indexes (p = 0.0052), than the animals in the other groups. The in silico analyses showed that there was an interaction between TTIp 56/287 and IR with interaction potential energy (IPE) of −1591.54 kJ mol−1 (±234.90), being lower than that presented by insulin and IR: −894.98 kJ mol−1 (±32.16). In addition, the presence of amino acids, type of binding and place of interaction other than insulin were identified. This study revealed the hypoglycemic effect of a bioactive molecule of protein origin from Tamarind seeds in a preclinical model of T2DM. Furthermore, the in silico analysis allowed the prediction of its binding in the IR, raising a new perspective for explaining TTI’s action on the glycemic response.