Therapeutic application of GPR119 ligands in metabolic disorders

• Published in: Diabetes, obesity & metabolism Vol. 20; no. 2; pp. 257 - 269
• Main Authors: Yang, Jin Won, Kim, Hyo Seon, Choi, Yong‐Won, Kim, Young‐Mi, Kang, Keon Wook
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2018; Wiley Subscription Services, Inc
• Subjects: Animals; Biomedical Research - methods; Biomedical Research - trends; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Drugs, Investigational - adverse effects; Drugs, Investigational - pharmacology; Drugs, Investigational - therapeutic use; Energy metabolism; Fatty liver; Gene Expression Regulation - drug effects; GPR119; Humans; Hypoglycemia; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Insulin; Intestine; Ligands; Lipotropic Agents - adverse effects; Lipotropic Agents - pharmacology; Lipotropic Agents - therapeutic use; Liver diseases; metabolic diseases; Metabolic Diseases - drug therapy; Metabolic Diseases - metabolism; Metabolic disorders; Metabolism; Models, Biological; Non-alcoholic Fatty Liver Disease - drug therapy; Non-alcoholic Fatty Liver Disease - metabolism; non‐alcoholic fatty liver disease; Organ Specificity; Pancreas; physiological/pharmacological effects; Receptors, G-Protein-Coupled - agonists; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Secretion; synthetic ligands; type 2 diabetes mellitus; type 2 diabetes mellitus; non-alcoholic fatty liver disease; GPR119; metabolic diseases; physiological/pharmacological effects; synthetic ligands
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.13062

GPR119 belongs to the G protein‐coupled receptor family and exhibits dual modes of action upon ligand‐dependent activation: pancreatic secretion of insulin in a glucose‐dependent manner and intestinal secretion of incretins. Hence, GPR119 has emerged as a promising target for treating type 2 diabetes mellitus without causing hypoglycaemia. However, despite continuous efforts by many major pharmaceutical companies, no synthetic GPR119 ligand has been approved as a new class of anti‐diabetic agents thus far, nor has any passed beyond phase II clinical studies. Herein, we summarize recent advances in research concerning the physiological/pharmacological effects of GPR119 and its synthetic ligands on the regulation of energy metabolism, and we speculate on future applications of GPR119 ligands for the treatment of metabolic diseases, focusing on non‐alcoholic fatty liver disease.