Glucagon-like peptide 1 (GLP-1)

Mol Metab. 2019 Dec:30:72-130. doi: 10.1016/j.molmet.2019.09.010. Epub 2019 Sep 30.

Authors

T D Müller¹, B Finan², S R Bloom³, D D'Alessio⁴, D J Drucker⁵, P R Flatt⁶, A Fritsche⁷, F Gribble⁸, H J Grill⁹, J F Habener¹⁰, J J Holst¹¹, W Langhans¹², J J Meier¹³, M A Nauck¹⁴, D Perez-Tilve¹⁵, A Pocai¹⁶, F Reimann⁸, D A Sandoval¹⁷, T W Schwartz¹⁸, R J Seeley¹⁷, K Stemmer¹⁹, M Tang-Christensen²⁰, S C Woods²¹, R D DiMarchi²², M H Tschöp²³

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: timo.mueller@helmholtz-muenchen.de.
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.

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.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Blood Glucose / metabolism
Diabetes Mellitus, Type 2 / metabolism
Gastric Inhibitory Polypeptide / metabolism
Glucagon-Like Peptide 1 / metabolism*
Glucagon-Like Peptide 1 / pharmacology*
Glucagon-Like Peptide-1 Receptor / metabolism
Glucose / metabolism
Humans
Hypoglycemic Agents / therapeutic use
Insulin / metabolism
Insulin Secretion
Insulin-Secreting Cells / metabolism
Obesity / metabolism
Receptors, Glucagon / metabolism

Substances

Blood Glucose
Glucagon-Like Peptide-1 Receptor
Hypoglycemic Agents
Insulin
Receptors, Glucagon
Gastric Inhibitory Polypeptide
Glucagon-Like Peptide 1
Glucose

Abstract

Publication types

MeSH terms

Substances

Grants and funding