Abstract
The identification of autophosphorylation of the insulin receptor as a pivotal component in the signal transduction induced by insulin, initiated the hunt to identify the tyrosine phosphatase(s) that were responsible for regulating dephosphorylation, and thus inactivation of the receptor. Compelling evidence for the existence of an insulin receptor specific PTP has come from the remarkable phenotype of the PTP1B deficient mouse. PTP1B deficient mice display an insulin sensitive phenotype and are able to maintain glucose homeostasis with about half the level of circulating insulin. In response to insulin administration PTP1B deficient mice have a significant increase in insulin receptor phosphorylation in liver and muscle compared to wild type controls. Unexpectedly these animals were also resistant to diet induced obesity. These observations strongly support PTP1B as a negative regulator of insulin action, thereby making it an ideal therapeutic target for intervention in type 2 diabetes and obesity.
Keywords: Protein Tyrosine Phosphatase, Diabetes and Obesity, autophosphorylation, tyrosine phosphatase, phenotype
Current Topics in Medicinal Chemistry
Title: Protein Tyrosine Phosphatase 1B: A Novel Target for Type 2 Diabetes and Obesity
Volume: 3 Issue: 7
Author(s): Chidambaram Ramachandran and Brian P. Kennedy
Affiliation:
Keywords: Protein Tyrosine Phosphatase, Diabetes and Obesity, autophosphorylation, tyrosine phosphatase, phenotype
Abstract: The identification of autophosphorylation of the insulin receptor as a pivotal component in the signal transduction induced by insulin, initiated the hunt to identify the tyrosine phosphatase(s) that were responsible for regulating dephosphorylation, and thus inactivation of the receptor. Compelling evidence for the existence of an insulin receptor specific PTP has come from the remarkable phenotype of the PTP1B deficient mouse. PTP1B deficient mice display an insulin sensitive phenotype and are able to maintain glucose homeostasis with about half the level of circulating insulin. In response to insulin administration PTP1B deficient mice have a significant increase in insulin receptor phosphorylation in liver and muscle compared to wild type controls. Unexpectedly these animals were also resistant to diet induced obesity. These observations strongly support PTP1B as a negative regulator of insulin action, thereby making it an ideal therapeutic target for intervention in type 2 diabetes and obesity.
Export Options
About this article
Cite this article as:
Ramachandran Chidambaram and Kennedy P. Brian, Protein Tyrosine Phosphatase 1B: A Novel Target for Type 2 Diabetes and Obesity, Current Topics in Medicinal Chemistry 2003; 3 (7) . https://dx.doi.org/10.2174/1568026033452276
DOI https://dx.doi.org/10.2174/1568026033452276 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
- 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
-
Review: Recent Clinical Trials in Epigenetic Therapy
Reviews on Recent Clinical Trials Glycoxidation of Low Density Lipoprotein in Impaired Glucose Tolerance: Implications for the Pathogenesis of Diabetic Vascular Disease
Vascular Disease Prevention (Discontinued) Potential Application of Plant-derived Bioengineered Human VEGF for Tissue Regeneration
Current Pharmaceutical Biotechnology Individual Differences in Novelty-Seeking and Behavioral Responses to Nicotine: A Review of Animal Studies
Current Drug Abuse Reviews Molecular Genetics and Epidemiology of Japanese Type 1 Diabetes
Current Pharmacogenomics Therapeutic Enzymes: Applications and Approaches to Pharmacological Improvement
Current Pharmaceutical Biotechnology Critical Questions for Preclinical Trials on Safety and Efficacy of Vascular Endothelial Growth Factor-Based Therapeutic Angiogenesis for Ischemic Stroke
CNS & Neurological Disorders - Drug Targets COPD Evaluation: Beyond the Airway Obstruction, a Follow Up
Current Respiratory Medicine Reviews Lipases in Medicine: An Overview
Mini-Reviews in Medicinal Chemistry Orexins and Gastrointestinal Functions
Current Protein & Peptide Science Functional Characterisation and Permeation Studies of Lyophilised Thiolated Chitosan Xerogels for Buccal Delivery of Insulin
Protein & Peptide Letters Strategies for the Assessment of Metabolic Profiles of Steroid Hormones in View of Diagnostics and Drug Monitoring: Analytical Problems and Challenges
Current Drug Metabolism Tumor-Intrinsic and Tumor-Extrinsic Factors Impacting Hsp90- Targeted Therapy
Current Molecular Medicine Social Determinants of Childhood Obesity: Beyond Individual Choices
Current Pediatric Reviews Epidemiology and Costs of Hypertension-related Disorders
Current Pharmaceutical Design Genetic Basis of Renal Mass in Rat Models
Current Hypertension Reviews mGlu2/3 Agonist-Induced Hyperthermia: An In Vivo Assay for Detection of mGlu2/3 Receptor Antagonism and its Relation to Antidepressant-Like Efficacy in Mice
CNS & Neurological Disorders - Drug Targets OMICs Technologies for Natural Compounds-based Drug Development
Current Topics in Medicinal Chemistry Expression and Characterisation of Recombinant Molecules in Transgenic Soybean
Current Pharmaceutical Design Emerging Concepts in Diabetes: Mitochondrial Dynamics and Glucose Homeostasis
Current Diabetes Reviews