BACKGROUND: GPR119 is a Gαs-protein-coupled receptor expressed predominantly in pancreatic islets and gastrointestinal tract in humans. OBJECTIVE/ METHODS: To review the available literature on GPR119 agonists. RESULTS: GPR119 de-orphanisation indicates two classes of possible endogenous agonists, phospholipids and fatty acid amides, with oleoylethanolamide and N-oleoyldopamine being the most potent. GPR119 agonists increase intracellular cAMP leading to increased glucose-dependent insulin secretion from pancreatic β-cells and incretin secretion from gut enteroendocrine cells. In various animal models of type 2 diabetes and obesity, orally available, potent, selective, synthetic GPR119 agonists: i) lower blood glucose without hypoglycaemia; ii) slow diabetes progression; and iii) reduce food intake and body weight. CONCLUSIONS: Oral GPR119 agonists may have the potential to achieve blood glucose control together with body weight loss in type 2 diabetics, an outcome only achievable currently with injectable glucagon-like peptide 1 receptor agonists.
BACKGROUND:GPR119 is a Gαs-protein-coupled receptor expressed predominantly in pancreatic islets and gastrointestinal tract in humans. OBJECTIVE/ METHODS: To review the available literature on GPR119 agonists. RESULTS:GPR119 de-orphanisation indicates two classes of possible endogenous agonists, phospholipids and fatty acid amides, with oleoylethanolamide and N-oleoyldopamine being the most potent. GPR119 agonists increase intracellular cAMP leading to increased glucose-dependent insulin secretion from pancreatic β-cells and incretin secretion from gut enteroendocrine cells. In various animal models of type 2 diabetes and obesity, orally available, potent, selective, synthetic GPR119 agonists: i) lower blood glucose without hypoglycaemia; ii) slow diabetes progression; and iii) reduce food intake and body weight. CONCLUSIONS: Oral GPR119 agonists may have the potential to achieve blood glucose control together with body weight loss in type 2 diabetics, an outcome only achievable currently with injectable glucagon-like peptide 1 receptor agonists.
Authors: Ivan N Tyurenkov; Denis V Kurkin; Dmitry A Bakulin; Elena V Volotova; Mikhail A Chafeev; Alexey V Smirnov; Evgeny I Morkovin Journal: Front Endocrinol (Lausanne) Date: 2017-07-07 Impact factor: 5.555
Authors: Ivan N Tyurenkov; Denis V Kurkin; Dmitry A Bakulin; Elena V Volotova; Evgeny I Morkovin; Mikhail A Chafeev; Ruben N Karapetian Journal: Front Endocrinol (Lausanne) Date: 2018-09-19 Impact factor: 5.555