title: GLP-1R and amylin agonism in metabolic disease: complementary mechanisms and future opportunities.
abstract: The discoveries of the incretin hormone glucagon-like peptide-1 (GLP-1) and the β-cell hormone amylin have translated into hormone-based therapies for diabetes. Both classes of molecules also exhibit weight-lowering effects and have been investigated for their anti-obesity potential. In the present review, we explore the mechanisms underlying the physiological and pharmacological actions of GLP-1 and amylin agonism. Despite their similarities (e.g. both molecular classes slow gastric emptying, decrease glucagon and inhibit food intake), there are important distinctions between the central and/or peripheral pathways that mediate their effects on glycaemia and energy balance. We suggest that understanding the similarities and differences between these molecules holds important implications for the development of novel, combination-based therapies, which are increasingly the norm for diabetes/metabolic disease. Finally, the future of GLP-1- and amylin agonist-based therapeutics is discussed.
authors.affiliation: Amylin Pharmaceuticals, Inc. San Diego, CA, USA. jonathan.roth@amylin.com
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Roth
authors.forename: Mary R
authors.initials: MR
authors.lastname: Erickson
authors.forename: Steve
authors.initials: S
authors.lastname: Chen
authors.forename: David G
authors.initials: DG
authors.lastname: Parkes
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000503:physiopathology; D004435:Eating / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000187:drug effects / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000819:agonists* / Q000378:metabolism; D008659:Metabolic Diseases / Q000188:drug therapy / Q000503:physiopathology; D009765:Obesity / Q000188:drug therapy / Q000503:physiopathology; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D058228:Islet Amyloid Polypeptide; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005934:Glucagon