Poster Presentation 2014 International Biophysics Congress

Phytochemicals for diabetes therapy (#639)

Ranjit Vijayan 1 , Shafna Asmy V.S. 1
  1. Department of Biology, United Arab Emirates University, Al Ain, Abu Dhabi, UAE

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by elevated levels of sugar in the blood.  An effective treatment for T2DM is still lacking due to the complex pathogenesis of the disorder. Several pathways are being studied currently to improve the action of insulin, to improve the ability of insulin secretion by pancreatic beta cells or to control the level of blood sugar. Diet is one of the major factors that lead to T2DM and may hold potential benefits as well. Studies have shown that phytochemicals from plants could provide a protective effect to individuals who may have or who may be susceptible to T2DM. However, the precise mechanism of the vast majority of these molecules is unknown.
A number of promising targets in diabetes related pathways - dipeptidyl peptidase 4 (DPP4), 5' AMP-activated protein kinase (AMPK), glucokinase and glycogen synthase kinase-3 (GSK-3) - were considered in this study. An initial collection of 30 phytochemicals known to have an effect on diabetes was selected for in silico screening. Several structures of the protein targets were also considered. Preliminary results show that some molecules - cyanidin diglucoside, proanthocyanidin, pellargonidin-3-rutinoside, epicatechin gallate and diadzin - may have the ability to interact favorably in the active site of several targets supporting the idea that many phytochemicals may interact with a diverse collection of targets. Cyanidin diglucoside, proanthocyanidin and pellargonidin-3-rutinoside are anthocyanidins and have a common core structure. In DPP4, these molecules appear to form salt bridges with Glu205 and Glu206, which plays a vital role in its inhibitory site. In AMPK, these molecules  interact with residues in its active site including Arg151, Lys169, His297 and Ser225. Work is currently in progress to characterize this further and to extend the study to a wider set of chemicals and protein targets.