Editor-in-Chief İlkay Küçükgüzel Associate Editor Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Quarterly (January-April-July-October) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2019 , Vol 23 , Issue 3
Vitamin D as a modulating agent of metformin and insulin in patients with type 2 diabetes
Fatemeh ABDI1,Monireh MOVAHEDI1,Mir Mohammad ALAVI NIKJE2,Laleh GHANEI3,Sako MIRZAIE4
1Department of Cellular and Molecular Biology, Islamic Azad University, Tehran North Branch, Tehran, Iran
2Department of Chemistry, Faculty of Science, Imam Khomeini International University, PO box 288
3Department of Endocrinology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
4Department of Biochemistry, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
DOI : 10.12991/jrp.2019.144 Diabetes, which is one of the most important health challenges for humankind, is associated with impaired glucose metabolism. Diabetes mellitus (DM) includes two major types of diabetes, type 1 (T1DM) and type 2 (T2DM). In this study, in the beginning, interventional and experimental studies were performed on 45 patients with T2DM, and the modulating effects of vitamin D were evaluated on the biochemical parameters of patients with the restricted diet, consuming metformin or insulin. With regard to our experimental results, the combination treatment of metformin/ vitamin D or insulin/ vitamin D can reduce the fasting blood sugar (FBS). A combination of vitamin D with insulin decreases the insulin resistance and raises the insulin sensitivity in patients with T2DM. The combination treatment of vitamin D and metformin led to a decrease in the level of mRNA of GLUT4, and also it’s trafficking from the cytosol to the plasma membrane. At the second phase of the present study, molecular dynamics (MD), molecular docking, MM/PBSA, and QM/MM were occupied to examine the structural behavior of VDR, in the free or ligand bound state, during 50 ns. The MD results exhibited that in the presence of metformin, the flexibility of residues comprising helix 12 from vitamin D-bound VDR was decreased. In addition, metformin decreased the radius of gyration of agonist-bound VDR. In addition, QM/MM results showed that metformin diminished the binding free energy between VDR and vitamin D. Our computational data demonstrated that metformin, in the presence of vitamin D, reinforces the interaction between VDR and its co-activator protein. Keywords : Diabetes mellitus type 2; metformin; vitamin D; molecular dynamics; vitamin D receptor; QM/MM
Marmara University