Fatty acid receptors as new therapeutic targets for diabetes.
G-protein-coupled receptors (GPCRs) are key regulators of several physiological functions. Their roles in cellular signal transduction have made them the target for majority of all currently prescribed drugs. Additionally, there are many orphan GPCRs that provide potential novel therapeutic targets. Several GPCRs are involved in metabolic regulation and glucose homeostasis such as GLP-1 receptor, glucagon receptor, adiponectin receptor and so on. Recently, free fatty acids (FFAs) have been demonstrated as ligands for orphan GPCRs and have been proposed to play a critical role in physiological glucose homeostasis. GPR40 and GPR120 are activated by medium and long-chain FFAs, whereas GPR41 and GPR43 can be activated by short-chain FFAs. GPR40, which is preferentially expressed in pancreatic beta-cells, mediates the majority of the effects of FFAs on insulin secretion. In this review, these findings and also critical analysis of these GPCRs as novel targets for diabetes are discussed.
Rayasam
Geetha Vani
GV
Metabolic Disorders, Department of Pharmacology, Research & Development (R&D III), Ranbaxy, Sector 18, Gurgaon, Haryana, India. geeta.rayasam@ranbaxy.com
Tulasi
Vamshi Krishna
VK
Davis
Joseph Alex
JA
Bansal
Vinay S
VS
D000818:Animals; D001419:Bacteria / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004040:Dietary Carbohydrates / Q000378:metabolism; D016503:Drug Delivery Systems; D015195:Drug Design; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005285:Fermentation; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007422:Intestines / Q000382:microbiology; D008099:Liver / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000008:administration & dosage / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C473103:FFAR2 protein, human; C473034:FFAR1 protein, human; C106262:FFAR3 protein, human; C519853:FFAR4 protein, human; C498007:FFAR4 protein, mouse; C519854:GPR119 protein, human