Abstract
Obesity and metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide. Obesity is the leading risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and non-alcoholic fatty liver disease. Obesity-associated insulin resistance, which is characterized by reduced uptake and utilization of glucose in muscle, adipose and liver tissues, is a key predictor of metabolic syndrome and T2DM. With increasing prevalence of obesity in adults and children, the need to identify and characterize potential targets for treating metabolic syndrome is imminent. Emerging evidence from animal models, clinical studies and cell lines studies suggest that protein tyrosine phosphatase 1B (PTP1B), an enzyme that negatively regulates insulin signaling, is likely to be involved in the pathways leading to insulin resistance. PTP1B is tethered to the cytosolic surface of endoplasmic reticulum (ER), an organelle that is responsible for folding, modification, and trafficking of proteins. Recent evidence links the disruption of ER homeostasis, referred to as ER stress, to the pathogenesis of obesity and T2DM. PTP1B has been recognized as an important player linking ER stress and insulin resistance in obese subjects. This review highlights recent advances in the research related to the role of PTP1B in signal transduction processes implicated in pathophysiology of obesity and type 2 diabetes, and focuses on the potential therapeutic exploitation of PTP1B inhibitors for the management of these conditions.
Keywords: Cell signaling, ER stress, insulin resistance, insulin signaling, leptin signaling, obesity, PTP1B, PTP1B inhibitors, type 2 diabetes.
Current Medicinal Chemistry
Title:Pharmacological Inhibition of Protein Tyrosine Phosphatase 1B: A Promising Strategy for the Treatment of Obesity and Type 2 Diabetes Mellitus
Volume: 20 Issue: 21
Author(s): E. Panzhinskiy, J. Ren and S. Nair
Affiliation:
Keywords: Cell signaling, ER stress, insulin resistance, insulin signaling, leptin signaling, obesity, PTP1B, PTP1B inhibitors, type 2 diabetes.
Abstract: Obesity and metabolic syndrome represent major public health problems, and are the biggest preventable causes of death worldwide. Obesity is the leading risk factor for type 2 diabetes mellitus (T2DM), cardiovascular diseases and non-alcoholic fatty liver disease. Obesity-associated insulin resistance, which is characterized by reduced uptake and utilization of glucose in muscle, adipose and liver tissues, is a key predictor of metabolic syndrome and T2DM. With increasing prevalence of obesity in adults and children, the need to identify and characterize potential targets for treating metabolic syndrome is imminent. Emerging evidence from animal models, clinical studies and cell lines studies suggest that protein tyrosine phosphatase 1B (PTP1B), an enzyme that negatively regulates insulin signaling, is likely to be involved in the pathways leading to insulin resistance. PTP1B is tethered to the cytosolic surface of endoplasmic reticulum (ER), an organelle that is responsible for folding, modification, and trafficking of proteins. Recent evidence links the disruption of ER homeostasis, referred to as ER stress, to the pathogenesis of obesity and T2DM. PTP1B has been recognized as an important player linking ER stress and insulin resistance in obese subjects. This review highlights recent advances in the research related to the role of PTP1B in signal transduction processes implicated in pathophysiology of obesity and type 2 diabetes, and focuses on the potential therapeutic exploitation of PTP1B inhibitors for the management of these conditions.
Export Options
About this article
Cite this article as:
Panzhinskiy E., Ren J. and Nair S., Pharmacological Inhibition of Protein Tyrosine Phosphatase 1B: A Promising Strategy for the Treatment of Obesity and Type 2 Diabetes Mellitus, Current Medicinal Chemistry 2013; 20 (21) . https://dx.doi.org/10.2174/0929867311320210001
DOI https://dx.doi.org/10.2174/0929867311320210001 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Adiponectin: Merely a Bystander or the Missing Link to Cardiovascular Disease?
Current Topics in Medicinal Chemistry Diabetes Trends in Hospitalized HIV-Infected Persons in the United States, 1994-2004
Current HIV Research Prevention of Ischemic Stroke: Antithrombotic Therapy in Cardiac Embolism
Current Drug Targets Evaluation of Risk Factors Associated with Diabetic Foot Ulcers in Saudi Arabia
Current Diabetes Reviews The Effects of Sevoflurane or Remifentanil on the Stress Response to Surgical Stimulus
Current Pharmaceutical Design Aetiology, Diagnosis and Treatment of Hydrops Foetalis
Current Pediatric Reviews The Impact of Metabolic Disease Associated with Metabolic Syndrome on Human Pregnancy
Current Pharmaceutical Biotechnology Biomarkers and Cellular Signal Detection for Alzheimer’s Disease, Stroke, and Immune System Mediated Disorders
Current Neurovascular Research Association of DRD2 TaqIA and DβH -1021C>T Gene Polymorphisms with Smoking Initiation and their Interaction with Serotonergic System Gene Polymorphisms
Current Pharmacogenomics and Personalized Medicine CXCR3, CXCR5, CXCR6, and CXCR7 in Diabetes
Current Drug Targets Transcription Factors in Autoimmune Diseases
Current Pharmaceutical Design The Role of AGEs and AGE Inhibitors in Diabetic Cardiovascular Disease
Current Drug Targets Editorial (Thematic Issue: Active Pregnancy - Benefits and Recommendations of Physical Activity and a Healthy Lifestyle Throughout Pregnancy and Postpartum)
Current Women`s Health Reviews Modifiable Risk Factors Associated with Alzheimer’s Disease with Special Reference to Sleep Disturbance
CNS & Neurological Disorders - Drug Targets Expression and Functions of Vasoactive Substances Regulated by Hypoxia-Inducible Factor-1 in Chronic Hypoxemia
Cardiovascular & Hematological Agents in Medicinal Chemistry Infection, its Treatment and the Risk for Stroke
Current Vascular Pharmacology Jumping on the Train of Personalized Medicine: A Primer for Non-Geneticist Clinicians: Part 2. Fundamental Concepts in Genetic Epidemiology
Current Psychiatry Reviews The Role of Polyunsaturated Fatty Acids (PUFA) in the Treatment of Dyslipidemias
Current Pharmaceutical Design The Role of Serum Calprotectin as a New Marker in Abdominal Aortic Aneurysms – A Preliminary Report
Current Pharmaceutical Biotechnology Some clinical applications of the electrochemical biosensors
Mini-Reviews in Medicinal Chemistry