Discovering the therapeutic potential of Naringenin in diabetes related to GLUT-4 and its regulatory factors: A computational approach

Abstract

This study explores the therapeutic potential of Naringenin, a natural flavonoid, in managing Type 2 Diabetes Mellitus (T2DM) by focusing on Glucose Transporter 4 (GLUT4) and related regulatory proteins that play a role in glucose and lipid metabolism. Through bioinformatics analysis, key proteins such as Carnitine palmitoyltransferase I, mitochondrial carnitine/acylcarnitine carrier protein, and PPARγ were identified, highlighting their importance in insulin sensitivity. Molecular docking results indicated that Naringenin has a strong binding affinity for GLUT4 and PPARγ, with binding energies of -8.18 kcal/mol and -8.21 kcal/mol, respectively. This suggests that Naringenin may modulate these proteins to enhance insulin sensitivity. In contrast, its weaker binding with Enhancer-Binding Protein Alpha points to Naringenin's selective efficacy among various targets. Molecular dynamics (MD) simulations conducted over 100 ns confirmed the stability of the GLUT4-Naringenin complex, showing a reduced RMSD of 1.25 nm and a more compact structure with a Radius of Gyration (Rg) value of 2.14 nm. However, Rho-related GTP exhibited increased instability upon Naringenin binding, indicating a potential inhibitory effect. Additionally, an in silico ADMET profile revealed Naringenin's favorable pharmacokinetics, including low hepatotoxicity, no mutagenic effects, and a high maximum tolerated dose, which supports its safety for drug development. In conclusion, Naringenin shows promising potential in enhancing glucose metabolism and insulin sensitivity, positioning it as a viable candidate for future preclinical and clinical studies in T2DM management. Future research should aim to validate these computational findings through experimental methods and investigate possible synergistic effects with existing antidiabetic medications to improve treatment outcomes.

Keywords

• Type 2 Diabetes Mellitus (T2DM)
• Glucose Transporter 4 (GLUT4)
• Carnitine palmitoyltransferase I
• Molecular dynamics (MD)
• PPARγ
• Flavonoid