Abstract
Glucagon and the glucagon-like peptides are derived from a common proglucagon precursor, and regulate energy homeostasis through interaction with a family of distinct G protein coupled receptors. Three proglucagon-derived peptides, glucagon, GLP-1, and GLP-2, play important roles in energy intake, absorption, and disposal, as elucidated through studies utilizing peptide antagonists and receptor knockout mice. The essential role of glucagon in the control of hepatic glucose production, taken together with data from studies employing glucagon antagonists, glucagon receptor antisense oligonucleotides, and glucagon receptor knockout mice, suggest that reducing glucagon action may be a useful strategy for the treatment of type 2 diabetes. GLP-1 secreted from gut endocrine cells controls glucose homeostasis through glucose-dependent enhancement of β-cell function and reduction of glucagon secretion and gastric emptying. GLP-1 administration is also associated with reduction of food intake, prevention of weight gain, and expansion of β-cell mass through stimulation of β-cell proliferation, and prevention of apoptosis. GLP-1R agonists, as well as enzyme inhibitors that prevent GLP-1 degradation, are in late stage clinical trials for the treatment of type 2 diabetes. Exenatide (Exendin-4) has been approved for the treatment of type 2 diabetes in the United States in April 2005. GLP-2 promotes energy absorption, inhibits gastric acid secretion and gut motility, and preserves mucosal epithelial integrity through enhancement of crypt cell proliferation and reduction of epithelial apoptosis. A GLP-2R agonist is being evaluated in clinical trials for the treatment of inflammatory bowel disease and short bowel syndrome. Taken together, the separate receptors for glucagon, GLP-1, and GLP-2 represent important targets for developing novel therapeutic agents for the treatment of disorders of energy homeostasis.
Keywords: Proglucagon, GLP-1, GLP-2, glucagon, g protein-coupled receptors, diabetes, intestinal disease, PGDP
Current Pharmaceutical Design
Title: Glucagon and Glucagon-Like Peptide Receptors as Drug Targets
Volume: 12 Issue: 14
Author(s): J. L. Estall and D. J. Drucker
Affiliation:
Keywords: Proglucagon, GLP-1, GLP-2, glucagon, g protein-coupled receptors, diabetes, intestinal disease, PGDP
Abstract: Glucagon and the glucagon-like peptides are derived from a common proglucagon precursor, and regulate energy homeostasis through interaction with a family of distinct G protein coupled receptors. Three proglucagon-derived peptides, glucagon, GLP-1, and GLP-2, play important roles in energy intake, absorption, and disposal, as elucidated through studies utilizing peptide antagonists and receptor knockout mice. The essential role of glucagon in the control of hepatic glucose production, taken together with data from studies employing glucagon antagonists, glucagon receptor antisense oligonucleotides, and glucagon receptor knockout mice, suggest that reducing glucagon action may be a useful strategy for the treatment of type 2 diabetes. GLP-1 secreted from gut endocrine cells controls glucose homeostasis through glucose-dependent enhancement of β-cell function and reduction of glucagon secretion and gastric emptying. GLP-1 administration is also associated with reduction of food intake, prevention of weight gain, and expansion of β-cell mass through stimulation of β-cell proliferation, and prevention of apoptosis. GLP-1R agonists, as well as enzyme inhibitors that prevent GLP-1 degradation, are in late stage clinical trials for the treatment of type 2 diabetes. Exenatide (Exendin-4) has been approved for the treatment of type 2 diabetes in the United States in April 2005. GLP-2 promotes energy absorption, inhibits gastric acid secretion and gut motility, and preserves mucosal epithelial integrity through enhancement of crypt cell proliferation and reduction of epithelial apoptosis. A GLP-2R agonist is being evaluated in clinical trials for the treatment of inflammatory bowel disease and short bowel syndrome. Taken together, the separate receptors for glucagon, GLP-1, and GLP-2 represent important targets for developing novel therapeutic agents for the treatment of disorders of energy homeostasis.
Export Options
About this article
Cite this article as:
Estall L. J. and Drucker J. D., Glucagon and Glucagon-Like Peptide Receptors as Drug Targets, Current Pharmaceutical Design 2006; 12 (14) . https://dx.doi.org/10.2174/138161206776873671
DOI https://dx.doi.org/10.2174/138161206776873671 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Targeting Chromatin Remodeling to Prevent Cardiovascular Disease in Diabetes
Current Pharmaceutical Biotechnology Roles of p38-MAPK in Insulin Resistant Heart: Evidence from Bench to Future Bedside Application
Current Pharmaceutical Design Advances in Drug Safety
Current Pharmaceutical Design Drug Induced QT Prolongation: Lessons from Congenital and Acquired Long QT Syndromes
Current Drug Targets - Cardiovascular & Hematological Disorders Pharmacogenetically Tailored Treatments for Heart Disease
Current Pharmaceutical Design Targeting Neurotrophic Signal Transduction Pathways in the Treatment of Mood Disorders
Current Signal Transduction Therapy Neuroimaging in Obsessive-Compulsive Disorder
Current Medical Imaging Spatial Correlations between the Vacuolation, Prion Protein (PrPsc) Deposits and the Cerebral Blood Vessels in Sporadic Creutzfeldt-Jakob Disease
Current Neurovascular Research Erythropoietin in Heart Failure and Other Cardiovascular Diseases: Hematopoietic and Pleiotropic Effects
Current Drug Targets - Cardiovascular & Hematological Disorders Postoperative Delirium
Current Drug Targets Characterization of Supraventricular Tachycardia in Infants: Clinical and Instrumental Diagnosis
Current Pharmaceutical Design NLRP3 Is Involved in Ischemia/Reperfusion Injury
CNS & Neurological Disorders - Drug Targets Experimental Animal Models of Myocardial Damage in Regenerative Medicine Studies Involving Adult Bone Marrow Derived Stem Cells: Ethical and Methodological Implications
Cardiovascular & Hematological Disorders-Drug Targets Macrophage Polarization as a Therapeutic Target in Myocardial Infarction
Current Drug Targets The Role of P2Y<sub>12</sub> Receptor and Activated Platelets During Inflammation
Current Drug Targets Preface: Vitamin D and QT Interval in Epilepsy: More than an Association?
Current Clinical Pharmacology Cardiovascular Magnetic Resonance Imaging: State of the Art
Current Cardiology Reviews Hypereosinophilic Syndrome, Churg-Strauss Syndrome and Parasitic Diseases: Possible Links between Eosinophilia and Thrombosis
Current Vascular Pharmacology Benefits of Exercise Training in Secondary Prevention of Coronary and Peripheral Arterial Disease
Vascular Disease Prevention (Discontinued) Adrenomedullin in Cardiovascular Disease: A Useful Biomarker, its Pathological Roles and Therapeutic Application
Current Protein & Peptide Science