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
  • 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.