<i>Salacia Reticulata</i> Extract Improves Insulin Sensitivity and Glucose Homeostasis by Activating Insulin Signaling and Glucagon-like Peptide-1 Modulation

This study evaluated the effects of <i>Salacia reticulata</i> on glucose metabolism, insulin signaling, and key metabolic markers in type 2 diabetes (T2D). We evaluated how <i>S. reticulata</i> influences the activity of major enzymes responsible for carbohydrate breakdown. <i>In vitro</i> studies on C2C12 cells also examined glucose uptake and insulin signaling pathway activation. Otsuka Long-Evans Tokushima Fatty (OLETF) rats were treated with <i>S. reticulata</i> (25 and 50 mg/kg body weight [bw]) or metformin (126 mg/kg bw) for 16 weeks<i>. S. reticulata</i> suppressed the activities of α-glucosidase and α-amylase while promoting insulin signaling pathways and glucose uptake in C2C12 myotubes. In OLETF rats, administration of <i>S. reticulata</i> markedly enhanced glucose tolerance, lowered fasting blood glucose and HbA1c levels, and significantly decreased the homeostatic model assessment for insulin resistance (HOMA-IR) index, reflecting improved insulin sensitivity. Western blot analysis revealed increased insulin receptor substrate-1, PI3K, Akt, and activated protein kinase (AMPK) phosphorylation, along with upregulated GLUT4 expression in skeletal muscle. Serum glucagon-like peptide-1 (GLP-1) and adiponectin levels were significantly elevated in the <i>S. reticulata</i>-treated groups, helping improve insulin action and systemic metabolic regulation. As a result, <i>S. reticulata</i> exerts beneficial effects on insulin sensitivity and glucose homeostasis by affecting key mechanisms such as insulin signaling, incretin dynamics, and adipokine modulation, reinforcing its value as a n'atural agent for treating T2D and associated metabolic issues.