Introducing the vitamins D3 and E as stabilizers of insulin hexamer form for regulated release, based on molecular dynamics simulation study

Mahdavian, Reza; Soleymani, Hossein; Ghorbani, Mohammad; Naderi-Manesh, Hossein

Introducing the vitamins D3 and E as stabilizers of insulin hexamer form for regulated release, based on molecular dynamics simulation study

Document Type : Original Research

Authors

Reza Mahdavian

Hossein Soleymani

Mohammad Ghorbani

Hossein Naderi-Manesh

Institute of Life Science, Tarbiat Modares University, Tehran, Iran

Abstract

Vitamins D and E are two common medicines for diabetes treatment. Among the main issues in this field is the release of insulin into the circulatory system. Increasing the stability of insulin hexamer is an evolving strategy in improving insulin secretion efficiency. Insulin protein is commonly found in three forms: monomer, dimer, and hexamer. In this study, for the first time, computational approaches were used to investigate the effect of vitamins D3 and E on the stability of insulin hexamer. The molecular docking results indicate six specific binding sites for these vitamins. These bind to the hydrophobic sites of insulin subunits due to their structural rings and hydrophobic properties. The G-mmpbsa analysis indicates the stabilizing role of both vitamins. The binding of these vitamins to the hexamer has significantly increased the binding energy between insulin subunits. Also, the number of hydrogen bonds between monomeric subunits of each insulin homodimer increased in the presence of the vitamins. It also significantly increases the number of internal hydrogen bonds of hexamer protein. Accordingly, vitamins D3 and E bind to and stabilize the insulin hexamer, resulting in a slower and more balanced insulin release as well as a longer half-life for the dimer in the bloodstream. These findings will pave the way to design a new strategy to regulate insulin release and increase its half-life in the blood for type II diabetes treatment. Besides, hexamer stabilization can be an effective treatment strategy for type I diabetes through slow release from an implanted biosensor system.

Keywords

Diabetes

G-mmpbsa

Insulin

molecular docking

Molecular dynamics simulation

Vitamins D3 and E

20.1001.1.23222115.1401.13.4.2.1

Subjects

Bioinformatics

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