Abstract
A variety of compounds containing an imidazoline ring have the ability to stimulate insulin secretion. Many of these also improve glycaemia in experimental models of type 2 diabetes and in man, suggesting that this class may be useful in the development of new orally active anti-diabetic drugs. However, the mechanisms by which imidazolines promote insulin secretion have not been clarified. The response does not appear to be due to the binding of ligands to either of the two major types of imidazoline receptor defined by pharmacological criteria (I1 and I2 sites) but may result from interaction with a novel imidazoline binding site. One such site has been identified in association with the ATP-sensitive potassium (KATP ) channel in the beta-cell and has been designated I3 . Electrophysiological and biochemical evidence suggest that the I 3 site may be intrinsic to the ion-conducting pore component, Kir6.2, of the KATP channel, but the effects of imidazoline ligands on insulin secretion can be dissociated from the regulation of Kir6.2. Indeed, there is increasing evidence that some imidazolines can control exocytosis directly, both in b-cells and in pancreatic alpha-cells. Thus, it is proposed that a further imidazoline binding site is primarily responsible for control of hormone secretion. Evidence is reviewed which suggests that this site occupies a central position within an amplification pathway that also mediates the effects of cAMP in the beta-cell. Characterisation of this site should provide the stimulus for the design of new insulin secretagogues that are devoid of KATP channel-blocking properties.
Keywords: Imidazoline binding, insulin secretagogues, glycaemia, diabetes, midazoline receptor, efarozan, moxonidine, phentolamine, harmane, rilmenidine, Imidazoline binding proteins
Current Pharmaceutical Design
Title: Imidazoline Binding Sites in the Endocrine Pancreas: Can They Fulfil Their Potential as Targets for the Development of New Insulin Secretagogues?
Volume: 7 Issue: 14
Author(s): Noel G. Morgan and Sue L.F. Chan
Affiliation:
Keywords: Imidazoline binding, insulin secretagogues, glycaemia, diabetes, midazoline receptor, efarozan, moxonidine, phentolamine, harmane, rilmenidine, Imidazoline binding proteins
Abstract: A variety of compounds containing an imidazoline ring have the ability to stimulate insulin secretion. Many of these also improve glycaemia in experimental models of type 2 diabetes and in man, suggesting that this class may be useful in the development of new orally active anti-diabetic drugs. However, the mechanisms by which imidazolines promote insulin secretion have not been clarified. The response does not appear to be due to the binding of ligands to either of the two major types of imidazoline receptor defined by pharmacological criteria (I1 and I2 sites) but may result from interaction with a novel imidazoline binding site. One such site has been identified in association with the ATP-sensitive potassium (KATP ) channel in the beta-cell and has been designated I3 . Electrophysiological and biochemical evidence suggest that the I 3 site may be intrinsic to the ion-conducting pore component, Kir6.2, of the KATP channel, but the effects of imidazoline ligands on insulin secretion can be dissociated from the regulation of Kir6.2. Indeed, there is increasing evidence that some imidazolines can control exocytosis directly, both in b-cells and in pancreatic alpha-cells. Thus, it is proposed that a further imidazoline binding site is primarily responsible for control of hormone secretion. Evidence is reviewed which suggests that this site occupies a central position within an amplification pathway that also mediates the effects of cAMP in the beta-cell. Characterisation of this site should provide the stimulus for the design of new insulin secretagogues that are devoid of KATP channel-blocking properties.
Export Options
About this article
Cite this article as:
Morgan G. Noel and Chan L.F. Sue, Imidazoline Binding Sites in the Endocrine Pancreas: Can They Fulfil Their Potential as Targets for the Development of New Insulin Secretagogues?, Current Pharmaceutical Design 2001; 7 (14) . https://dx.doi.org/10.2174/1381612013397366
DOI https://dx.doi.org/10.2174/1381612013397366 |
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
-
A Comprehensive Review on Preclinical Diabetic Models
Current Diabetes Reviews Structural Perspectives and Advancement of SGLT2 Inhibitors for the Treatment of Type 2 Diabetes
Current Diabetes Reviews Non Genomic Modulation of Ligand Gated Ionotropic Receptors by Thyroid Hormones
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Modeling Loss of Microvascular Wall Homeostasis during Glycocalyx Deterioration and Hypertension that Impacts Plasma Filtration and Solute Exchange
Current Neurovascular Research The role of vitamin D towards immune tolerance in white adipose tissue (WAT)
Endocrine, Metabolic & Immune Disorders - Drug Targets Mitochondrial Membrane Lipids in Life and Death and their Molecular Modulation by Diet: Tuning the Furnace
Current Drug Targets The Pathogenesis of Susceptibility to Acute Kidney Injury in the Elderly
Current Aging Science Induction of Propranolol Metabolism by Ginkgo biloba Extract EGb 761 in Rats
Current Drug Metabolism Editorial [Hot Topic: Molecular Targeted Therapy of Gastrointestinal Cancer (Guest Editor: Marcus W. Wiedmann)]
Current Cancer Drug Targets The Chemokine System as a Therapeutic Target in Autoimmune Thyroid Diseases: A Focus on the Interferon-γ Inducible Chemokines and their Receptor
Current Pharmaceutical Design Editorial [Hot Topic: Anti-Lipogenesis as a Novel Strategy for Cancer Therapy (Guest Editors: Jianghua Liu and Deliang Cao)]
Recent Patents on Anti-Cancer Drug Discovery Sphingolipid Metabolism and Leukemia: A Potential for Novel Therapeutic Approaches
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Endocrine, Metabolic & Immune Disorders - Drug Targets Targeting Angiogenesis in Gastro-Intestinal Non Colorectal Cancers; A Review
Current Angiogenesis (Discontinued) The Impact of Docosahexaenoic Acid on Alzheimer’s Disease: Is There a Role of the Blood-Brain Barrier?
Current Clinical Pharmacology Will Sodium Intake Reduction Improve Cardiovascular Outcomes in the General Population? A Critical Review of Current Evidence
Current Hypertension Reviews A Review of Micro/Nano Welding and Its Future Developments
Recent Patents on Nanotechnology Diabetic CVD – Soluble Epoxide Hydrolase as A Target
Cardiovascular & Hematological Agents in Medicinal Chemistry New Frontiers in Cystic Fibrosis Therapy: The Case of Stem Cells
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) Nitrogen-Containing Bisphosphonates and Cancer Immunotherapy
Current Pharmaceutical Design