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.
摘要：
这项研究的目的是评估从罗望子种子（TTI）中分离的胰蛋白酶抑制剂在T2DM实验模型中的降血糖作用以及TTI56/287构象模型与胰岛素受体（IR）之间的计算机相互作用。诱导T2DM后，将15只雄性Wistar大鼠随机分为三组（n=5）：不治疗的1-T2DM组；充足饮食治疗的2-T2DM组和TTI治疗的3-T2DM（25mg/kg），10天。分析胰岛素血症和空腹血糖，计算HOMA-IR和HOMA-β。用TTI处理的动物组呈现较低的空腹葡萄糖浓度(p=0.0031)和较低的HOMA-IR指数(p=0.0432)。随着较高的HOMA-β指数(p=0.0052)，比其他组的动物。计算机分析表明，TTIP56/287与IR之间存在相互作用，相互作用势能（IPE）为-1591.54kJmol-1（±234.90），低于胰岛素和IR：-894.98kJmol-1（±32.16）。此外,氨基酸的存在，确定了胰岛素以外的结合类型和相互作用位置.这项研究揭示了罗望子种子蛋白质来源的生物活性分子在T2DM临床前模型中的降血糖作用。此外，计算机模拟分析允许预测其在IR中的结合，为解释TTI对血糖反应的作用提供了新的视角。
