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 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
-
Socioeconomic Position and Type 2 Diabetes Mellitus in Europe 1999- 2009: a Panorama of Inequalities
Current Diabetes Reviews Factors Predisposing to Hypertension in Subjects Formerly Born Preterm: Renal Impairment, Arterial Stiffness, Endothelial Dysfunction or Something Else?
Current Hypertension Reviews Applications of Extremophilic Archaeal Lipids in the Field of Nanocarriers for Oral/Topical Drug Delivery
Current Biotechnology High Serum Alkaline Phosphatase Levels in Relation to Multi-Cerebral Microbleeds in Acute Ischemic Stroke Patients with Atrial Fibrillation and/or Rheumatic Heart Disease
Current Neurovascular Research Insulin Resistance as a Therapeutic Target for Improved Endothelial Function:Metformin
Current Drug Targets - Cardiovascular & Hematological Disorders Evaluation and Management of Children with Thyrotoxicosis
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Role of Phytochemicals in the Prevention of Menopausal Bone Loss: Evidence from In Vitro and In Vivo, Human Interventional and Pharmacokinetic Studies
Current Medicinal Chemistry Adult Stem Cells and Skeletal Muscle Regeneration
Current Gene Therapy Editorial (Thematic Issue: Global Clinical Trials, Research, Regulations and Education)
Applied Clinical Research, Clinical Trials and Regulatory Affairs Perspectives on the Development of Antioxidant Antiepileptogenic Agents
Mini-Reviews in Medicinal Chemistry Accessing the Blood-Brain Barrier to Treat Brain Disorders
Current Nanomedicine A Perspective on the Current Strategies for the Treatment of Obesity
Current Drug Targets - CNS & Neurological Disorders Does Brachial Blood Pressure Need to Predict Cardiovascular Outcomes in End Stage Renal Disease? An Update
Current Hypertension Reviews Molecular Imaging of Vascular Inflammation
Current Pharmaceutical Design Non-Genotoxic p53-Activators and their Significance as Antitumor Therapy of Future
Current Medicinal Chemistry Exploring N<sup>1</sup>-p-Fluorobenzyl-Cymserine as an Inhibitor of 5-Lipoxygenase as a Candidate for Type 2 Diabetes and Neurodegenerative Disorder Treatment
CNS & Neurological Disorders - Drug Targets Photo-Affinity Labeling Strategies in Identifying the Protein Ligands of Bioactive Small Molecules: Examples of Targeted Synthesis of Drug Analog Photoprobes
Combinatorial Chemistry & High Throughput Screening Exploiting HPV-Induced Carcinogenesis for a Rational Drug Development in Cervical Cancer
Current Cancer Drug Targets Hypertension, Prehypertension and Blood Pressure Related Diseases
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Medulloblastoma: Role of Developmental Pathways, DNA Repair Signaling, and Other Players
Current Molecular Medicine