Abstract
Modern societies have moved from famine to feast and obesity and its co-morbidities now sweep the world as a global epidemic. Numerous scientific laboratories and pharmaceutical companies have taken the challenge and are now exploiting novel molecular targets for treatment of obesity. The pre-proglucagon system constitutes interesting candidates as potential targets for new anti-obesity drugs. In the periphery, pre-proglucagon derived peptides, Glucagon-Like Peptide-1 (GLP-1), Glucagon-Like Peptide-2 (GLP-2) and oxyntomodulin (OXM) are involved in a wide variety of physiological functions, including glucose homeostasis, gastric emptying, intestinal growth, insulin secretion as well as the regulation of food intake. Peripheral administration of GLP-1 derivatives and analogues to both rodents and man have shown promising effects on food intake and body weight suggesting that such therapies constitute potential anti-obesity treatment. In the central nervous system, pre-proglucagon and hence GLP-1, GLP-2 and OXM are exclusively found in a small population of nerve cells in the nucleus of the solitary tract. These constitute a neural pathway linking the “viscerosensory” brainstem to hypothalamic nuclei involved in energy homeostasis. Intracerebroventricular administration of all of the three derived peptides robustly decrease food intake. It is evident that central GLP-1 agonism probably in combination with GLP-2 and / or OXM agonism constitute a potential pharmacological tool to reduce food intake and maybe also enhance energy expenditure. This and other aspects of the current state of the role of central pre-proglucagon in energy homeostasis are reviewed.
Keywords: pre-proglucagon derived peptides, obesity, co-morbidities, glucagon-like peptide-1, gastric emptying
Current Pharmaceutical Design
Title: Central Pre-proglucagon Derived Peptides: Opportunities for Treatment of Obesity
Volume: 9 Issue: 17
Author(s): Philip J. Larsen, Niels Vrang and Mads Tang-Christensen
Affiliation:
Keywords: pre-proglucagon derived peptides, obesity, co-morbidities, glucagon-like peptide-1, gastric emptying
Abstract: Modern societies have moved from famine to feast and obesity and its co-morbidities now sweep the world as a global epidemic. Numerous scientific laboratories and pharmaceutical companies have taken the challenge and are now exploiting novel molecular targets for treatment of obesity. The pre-proglucagon system constitutes interesting candidates as potential targets for new anti-obesity drugs. In the periphery, pre-proglucagon derived peptides, Glucagon-Like Peptide-1 (GLP-1), Glucagon-Like Peptide-2 (GLP-2) and oxyntomodulin (OXM) are involved in a wide variety of physiological functions, including glucose homeostasis, gastric emptying, intestinal growth, insulin secretion as well as the regulation of food intake. Peripheral administration of GLP-1 derivatives and analogues to both rodents and man have shown promising effects on food intake and body weight suggesting that such therapies constitute potential anti-obesity treatment. In the central nervous system, pre-proglucagon and hence GLP-1, GLP-2 and OXM are exclusively found in a small population of nerve cells in the nucleus of the solitary tract. These constitute a neural pathway linking the “viscerosensory” brainstem to hypothalamic nuclei involved in energy homeostasis. Intracerebroventricular administration of all of the three derived peptides robustly decrease food intake. It is evident that central GLP-1 agonism probably in combination with GLP-2 and / or OXM agonism constitute a potential pharmacological tool to reduce food intake and maybe also enhance energy expenditure. This and other aspects of the current state of the role of central pre-proglucagon in energy homeostasis are reviewed.
Export Options
About this article
Cite this article as:
Larsen J. Philip, Vrang Niels and Tang-Christensen Mads, Central Pre-proglucagon Derived Peptides: Opportunities for Treatment of Obesity, Current Pharmaceutical Design 2003; 9 (17) . https://dx.doi.org/10.2174/1381612033454775
DOI https://dx.doi.org/10.2174/1381612033454775 |
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
-
Anti-Inflammatory Role of Thyroid Hormones on Rat Air Pouch Model of Inflammation
Inflammation & Allergy - Drug Targets (Discontinued) Inflammation and Mood Disorders: Proinflammatory Cytokines and the Pathogenesis of Depression
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry 2-Mercapto Benzothiazole Derivatives: As Potential Leads for the Diabetic Management
Medicinal Chemistry Resistin and Oxidative Stress in Non-Diabetic Obstructive Sleep Apnea Patients with Nocturnal Hypertension
Current Respiratory Medicine Reviews Modulation of Cardiovascular Remodeling with Statins: Fact or Fiction?
Current Vascular Pharmacology Surgery for Severe Obesity: Indications, Techniques, Mechanisms of Weight Loss and Diabetes Resolution
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Can Imaging Techniques Identify Smoking-Related Cardiovascular Disease?
Current Pharmaceutical Design Anti-Inflammatory Properties of Drugs from saffron crocus
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Cardioembolic Stroke: Clinical Features, Specific Cardiac Disorders and Prognosis
Current Cardiology Reviews Pitavastatin and 4-Hydroxy-3-Methoxyacetophenone (HMAP) Reduce Cognitive Dysfunction in Vascular Dementia During Experimental Diabetes
Current Neurovascular Research Editorial [ Cardiovascular Risk Factor Modification: A sine qua non in the Management of Vascular Surgery Patients ]
Current Vascular Pharmacology Three-Dimensional Ultrasound in Fetal Size and Growth Assessment
Current Medical Imaging Energy Metabolism, Adult Neurogenesis and their Possible Roles in Alzheimer’s Disease: A Brief Overview
Current Topics in Medicinal Chemistry A Systematic Review on Effect of Canagliflozin in Special Population
Current Diabetes Reviews Season of Birth Effects on Reproduction in Women
Current Women`s Health Reviews Diabetes in Racial and Ethnic Minorities in the United States: Individualizing Approaches to Diagnosis and Management
Current Diabetes Reviews Inflammatory Mechanisms and Redox Status in Periodontal and Cardiometabolic Diseases: Effects of Adjunctive Nutritional Antioxidants and Statins
Infectious Disorders - Drug Targets Clinical Use of Real-Time Continuous Glucose Monitoring
Current Diabetes Reviews Herbs for Effective Treatment of Diabetes Mellitus Wounds: Medicinal Chemistry and Future Therapeutic Options
Mini-Reviews in Medicinal Chemistry Obstructive Sleep Apnea and Type 2 Diabetes: Dual Interaction
Current Respiratory Medicine Reviews