Glucagon-like peptide 1 (GLP-1)

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

Contributors

T.D. Müller

Journal

Journal ID (nlm-ta): Mol Metab

Journal ID (iso-abbrev): Mol Metab

Title: Molecular Metabolism

Publisher: Elsevier

ISSN (Electronic): 2212-8778

Publication date PMC-release: 30 September 2019

Publication date Collection: December 2019

Publication date (Electronic): 30 September 2019

Volume: 30

Pages: 72-130

Affiliations

[1 ]Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany

[2 ]German Center for Diabetes Research (DZD), Neuherberg, Germany

[3 ]Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, Tübingen, Germany

[4 ]Novo Nordisk Research Center Indianapolis, Indianapolis, IN, USA

[5 ]Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK

[6 ]Division of Endocrinology, Duke University Medical Center, Durham, NC, USA

[7 ]The Department of Medicine, Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Ontario, M5G1X5, Canada

[8 ]SAAD Centre for Pharmacy & Diabetes, Ulster University, Coleraine, Northern Ireland, UK

[9 ]Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany

[10 ]Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Tübingen, Germany

[11 ]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

[12 ]Institute of Diabetes, Obesity and Metabolism, Department of Psychology, University of Pennsylvania, Philadelphia, PA, 19104, USA

[13 ]Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard University, Boston, MA, USA

[14 ]Novo Nordisk Foundation Center for Basic Metabolic Research, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

[15 ]Physiology and Behavior Laboratory, ETH Zurich, Schwerzenbach, Switzerland

[16 ]Diabetes Division, St Josef Hospital, Ruhr-University Bochum, Bochum, Germany

[17 ]Diabetes Center Bochum-Hattingen, St Josef Hospital (Ruhr-Universität Bochum), Bochum, Germany

[18 ]Department of Internal Medicine, University of Cincinnati-College of Medicine, Cincinnati, OH, USA

[19 ]Cardiovascular & ImmunoMetabolism, Janssen Research & Development, Welsh and McKean Roads, Spring House, PA, 19477, USA

[20 ]Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA

[21 ]Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, DL-2200, Copenhagen, Denmark

[22 ]Department of Biomedical Sciences, University of Copenhagen, DK-2200, Copenhagen, Denmark

[23 ]Obesity Research, Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark

[24 ]Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, Cincinnati, OH, USA

[25 ]Department of Chemistry, Indiana University, Bloomington, IN, USA

[26 ]Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany

[27 ]Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany

Author notes

[∗ ]Corresponding author. Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Neuherberg, Germany. timo.mueller@ 123456helmholtz-muenchen.de

Article

Publisher ID: S2212-8778(19)30913-5

DOI: 10.1016/j.molmet.2019.09.010

PMC ID: 6812410

Copyright statement: © 2019 The Authors

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Categories

Subject: Review