Effect of Terminalia catappa in High-Fat Diet/STZ-Induced Insulin Resistance: Deciphering Possible Role of GLUT4

Insulin resistance (IR) is reduced responsiveness of peripheral tissues, such as skeletal muscle, liver, and adipose tissue, to insulin action. Since skeletal muscle is most liable for the majority of glucose uptake, any disturbance in GLUT4 translocation becomes a major contributor to impaired glucose homeostasis. The current study examined the therapeutic potential of Terminalia catappa (TC) leaf extract in reducing insulin resistance with a focus on GLUT4 expression in skeletal muscle. The extract was first analysed using LC-MS to identify its phytochemical constituents, and the major compounds were further subjected to in silico docking using Schrodinger Glide to assess their interaction with the GLUT4 protein (PDB ID: 7WSN). The Male Sprague-Dawley rats were given a high-fat diet for eight weeks before receiving an intraperitoneal injection of streptozotocin (35 mg/kg) to induce insulin resistance. The dose of 400 and 800 mg/kg of TC extract were given daily orally. When compared to the HFD+STZ group, treatment with TC significantly lowered fasting blood glucose levels, enhanced circulating insulin concentrations, and decreased HOMA-IR values. In the oral glucose tolerance test, treated animals also showed improved glucose clearance. Increased GLUT4 expression in skeletal muscle was also found by Western blot analysis, suggesting that insulin signalling pathways have been restored. All of these findings point to Terminalia catappa potential as a natural treatment option for metabolic diseases by suggesting that it reduces insulin resistance by boosting GLUT4-mediated glucose uptake and enhancing metabolic homeostasis.