title: Apelin receptors: From signaling to antidiabetic strategy.
abstract: The G protein-coupled receptor APJ and its cognate ligand, apelin, are widely expressed throughout human body. They are implicated in different key physiological processes such as angiogenesis, cardiovascular functions, fluid homeostasis and energy metabolism regulation. On the other hand, this couple ligand-receptor is also involved in the development and progression of different pathologies including diabetes, obesity, cardiovascular disease and cancer. Recently, a new endogenous peptidic ligand of APJ, named Elabela/Toddler, has been identified and shown to play a crucial role in embryonic development. Whereas nothing is yet known regarding Elabela/Toddler functions in adulthood, apelin has been extensively described as a beneficial adipokine regarding to glucose and lipid metabolism and is endowed with anti-diabetic and anti-obesity properties. Indeed, there is a growing body of evidence supporting apelin signaling as a novel promising therapeutic target for metabolic disorders (obesity, type 2 diabetes). In this review, we provide an overview of the pharmacological properties of APJ and its endogenous ligands. We also report the activity of peptidic and non-peptidic agonists and antagonists targeting APJ described in the literature. Finally, we highlight the important role of this signaling pathway in the control of energy metabolism at the peripheral level and in the central nervous system in both physiological conditions and during obesity or diabetes.
authors.affiliation: Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Chaves-Almagro
authors.affiliation: Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France.
authors.forename: I
authors.initials: I
authors.lastname: Castan-Laurell
authors.affiliation: Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Dray
authors.affiliation: Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Knauf
authors.affiliation: Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France.
authors.forename: P
authors.initials: P
authors.lastname: Valet
authors.affiliation: Institute of Cardiovascular and Metabolic Diseases (I2MC) - INSERM U1048, University Paul Sabatier, Toulouse, France. Electronic address: bernard.masri@inserm.fr.
authors.forename: B
authors.initials: B
authors.lastname: Masri
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008969:Molecular Sequence Data; D009765:Obesity / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled
keywords: APJ; Adipokine; Apelin; Diabetes; Elabela; G protein-coupled receptor; Metabolism; Obesity; Signaling; Toddler