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GPR21, A novel target for Type 2 Diabetes


The orphan G-protein coupled receptor, GPR21, has emerged as a novel target for the treatment of Type 2 Diabetes (T2D). GPR21 knockout mice, fed a on high fat diet, demonstrate increased insulin sensitivity and glucose tolerance when compared to wild-type littermates, prompting further investigation into this receptor.

The G-protein signalling capabilities of GPR21 have been established through a functional FRET-based assay, and indicate constitutive activity, which increases when coupled with specific G-proteins. Preliminary results indicate that overexpression of GPR21 in mammalian cells negatively impacts the insulin signalling pathway, an effect which may be augmented by native ligands present in serum. A structural homology model of GPR21 has also been developed to design novel, small molecule ligands to bind to this receptor. One such compound, restores the signalling capabilities of insulin in cells overexpressing GPR21, paving the way to develop a novel therapeutic for T2D.
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