Development of novel ligands for peptide GPCRs.
Incretin based glucagon-like peptide-1 receptor (GLP-1R) agonists which target a G-protein coupled receptor (GPCR) are currently used in the treatment of type 2 diabetes. This review focuses on GPCRs from pancreatic β-cells, including GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon, somatostatin, pancreatic polypeptide (PP), cholecystokinin (CCK), peptide YY (PYY), oxyntomodulin (OXM) and ghrelin receptors. In addition, fatty acids GPCRs are thought to have an increasing role in regulating peptide secretions namely short fatty acids GPCR (GPR41, GPR43), medium chain fatty acid GPCR (GPR84), long chain fatty acid GPCR (GPR40, GPR120) and cannabinoid-like GPCR (GPR55, GPR119). Several pre-clinical and clinical trials are currently ongoing in peptide GPCR based therapies, including dual and triple agonist peptides which activate two or more GPCRs simultaneously.
Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, United Kingdom.
Brian M
BM
Moran
Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, United Kingdom.
Aine M
AM
McKillop
Biomedical Sciences Research Institute, School of Biomedical Sciences, Ulster University, Cromore Road, Coleraine BT52 1SA, Northern Ireland, United Kingdom. Electronic address: fpm.oharte@ulster.ac.uk.
Finbarr Pm
FP
O'Harte
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D015195:Drug Design; D005227:Fatty Acids; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D054795:Incretins / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008024:Ligands; D010455:Peptides / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
D005227:Fatty Acids; D007004:Hypoglycemic Agents; D054795:Incretins; D008024:Ligands; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D000097789:Glucagon-Like Peptide-1 Receptor Agonists