TURMERIC (CURCUMA LONGA) EXTRACT ENHANCES FIBROBLAST GROWTH FACTOR 21 (FGF21) SENSITIVITY AND MITIGATES SUPPRESSOR OF CYTOKINE SIGNALING PROTEIN-3 (SOCS-3)-INDUCED INSULIN RESISTANCE IN TYPE 2 DIABETIC RATS

Abstract

Type 2 diabetes mellitus (T2DM) is a disorder characterized by insulin resistance, hyperglycemia, and inflammation. Fibroblast growth factor 21 (FGF21) plays a crucial role in glucose and lipid metabolism but is often dysregulated in T2DM due to FGF21 resistance, linked to reduced β-Klotho expression. Additionally, unregulated blood glucose activates inflammatory pathways, increasing suppressor of cytokine signaling protein-3 (SOCS-3), which contributes to insulin resistance. This study investigates the potential of turmeric (Curcuma longa) extract in enhancing FGF21 sensitivity and mitigating SOCS-3-induced insulin resistance in T2DM. Thirty male Wistar rats were randomly assigned into five groups: normal control (NC), diabetic control (DC), diabetic rats treated with turmeric extract (100 mg/kg and 200 mg/kg), and diabetic rats treated with metformin (500 mg/kg). T2DM was induced by administering 10% fructose for 14 days, followed by streptozotocin (50 mg/kg) intraperitoneally. Turmeric extract exhibited a time-dependent hypoglycemic effect, significantly (P < 0.05) reducing blood glucose from the second week, with 200 mg/kg showing the greatest effect. Insulin levels increased significantly (P < 0.05), and HOMA-IR decreased in all treated groups, indicating improved insulin sensitivity. Gene expression analysis showed a significant (P < 0.05) upregulation of GLUT-4 and β-Klotho, along with downregulation of SOCS-3 and FGF21.Turmeric extract improves glucose metabolism through enhanced insulin sensitivity, GLUT-4 activation, SOCS-3 suppression, and restoration of FGF21 signaling via β-Klotho upregulation.