2. Academic Validation
  3. Glucagon-like peptide 1 (GLP-1)

Glucagon-like peptide 1 (GLP-1)

  • Mol Metab. 2019 Dec:30:72-130. doi: 10.1016/j.molmet.2019.09.010.
T D Müller 1,  B Finan 2,  S R Bloom 3,  D D'Alessio 4,  D J Drucker 5,  P R Flatt 6,  A Fritsche 7,  F Gribble 8,  H J Grill 9,  J F Habener 10,  J J Holst 11,  W Langhans 12,  J J Meier 13,  M A Nauck 14,  D Perez-Tilve 15,  A Pocai 16,  F Reimann 8,  D A Sandoval 17,  T W Schwartz 18,  R J Seeley 17,  K Stemmer 19,  M Tang-Christensen 20,  S C Woods 21,  R D DiMarchi 22,  M H Tschöp 23
Affiliations

Affiliations

  • 1 Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany. Electronic address: [email protected].
  • 2 Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA.
  • 3 Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK.
  • 4 Division of Endocrinology, Duke University Medical Center, Durham, NC, USA.
  • 5 The Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Ontario, M5G1X5, Canada.
  • 6 SAAD Centre for Pharmacy & Diabetes, Ulster University, Coleraine, Northern Ireland, UK.
  • 7 German Center for Diabetes Research (DZD), Neuherberg, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany.
  • 8 Metabolic Research Laboratories and Medical Research Council Metabolic Diseases Unit, Wellcome Trust-Medical Research Council, Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge, Cambridge, CB2 0QQ, UK.
  • 9 Institute of Diabetes, Obesity and Metabolism, Department of Psychology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • 10 Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard University, Boston, MA, USA.
  • 11 Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • 12 Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland.
  • 13 Diabetes Division, St Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
  • 14 Diabetes Center Bochum-Hattingen, St Josef Hospital (Ruhr-Universität Bochum), Bochum, Germany.
  • 15 Department of Internal Medicine, University of Cincinnati-College of Medicine, Cincinnati, OH, USA.
  • 16 Cardiovascular & ImmunoMetabolism, Janssen Research & Development, Welsh and McKean Roads, Spring House, PA, 19477, USA.
  • 17 Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
  • 18 Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DL-2200, Copenhagen, Denmark; Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark.
  • 19 Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.
  • 20 Obesity Research, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
  • 21 Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA.
  • 22 Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA; Department of Chemistry, Indiana University, Bloomington, IN, USA.
  • 23 German Center for Diabetes Research (DZD), Neuherberg, Germany; Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany; Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany.
PMID: 31767182 DOI: 10.1016/j.molmet.2019.09.010
Abstract

Background: The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of Insulin secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and Apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 Receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity.

Scope of review: In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases.

Major conclusions: Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders.

Keywords

Diabetes; GLP-1; Glucagon; Incretin; Insulin; Obesity.

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