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Abstract

INSILCO STUDIES ON MEMBRANE RECEPTORS OF TYPE 2 DIABETES MILLETUS

Priyanka Tiruveedhula*, Anita P. Muttagi, Kusum Paul

ABSTRACT

Type 2 Diabetes Milletus (T2DM) is a metabolic disease in which carbohydrate and lipid metabolism is improperly regulated by insulin. Nevertheless, defective insulin secretion emerges as a main culprit in Type 2 diabetes with lifestyle factors via obesity which accounts for current dramatic increase in Type 2 diabetes. Currently there is still lack of efficient drugs against this disease hence discovery of potential compounds targeting the disease has become a vital approach for antidiabetic drug development. G-Protein coupled receptors (GPCR) plays main role in T2DM. GPR40 and its related homologous proteins such as GPR119 and GPR120 which are highly expressed in pancreas are reported as the vital components in fatty acid augmentation of insulin secretion. In this study the structures of three GPCR receptors are predicted by ab-initio modelling and modelled by using some model building techniques which are validated by various tools. In order to explore the activity of these three receptors, molecular dynamic simulations are performed and leading to molecular docking studies with some structurally diverse ligands which are screened by pharmacodynamic properties, the differences in their binding modes are investigated by the docking interactions and identified the compounds which exhibits good antidiabetic activity based on virtual screening. Furthermore pharmacophore models are built based on the docking interactions to identify the structure based ligand binding properties. As per the studies done few compound shows good effective interactions with these GPCR receptors, which can be further used for the in vitro studies and can be proved as a potential drugs used for the treatment of T2DM.

Keywords: Type 2 Diabetes,GPR40,GPR120,GPR119,novel targets of diabetes, targets of diabetes, Insilco studies on diabetes.


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