Background: GPR40, an orphan G-protein coupled receptor that is activated by medium
and long-chain fatty acids and is highly expressed in pancreatic islets, adipose depots and the
gastrointestinal tract are involved in energy source recognition, absorption, storage and/or metabolism.
Since its deorphanization in 2003, G-protein-coupled receptor GPR40 has emerged as a potential target
for type II diabetes because it has been hypothesized to participate in the adverse effects of chronic
fatty acid exposure on function of β-cell.
Results: This signifies that G-protein-coupled receptors have recently emerged as novel therapeutic
targets in metabolic diseases, such as diabetes, obesity and the metabolic syndrome. Therefore it seems
natural that GPR40 represents a potentially attractive target to best meet the need for novel treatments
for Type II diabetes.
Conclusion: This review describes recent advances and novel drug discovery approaches in the
antidiabetic area, focusing on GPR40 modulators which have been synthesized till date and their
Structure-Activity Relationship (SAR).