Abstract
Essential hypertension is an insulin resistant state. Early insulin signaling steps are impaired in essential hypertension and a large body of data suggests that there is a crosstalk at multiple levels between the signal transduction pathways that mediate insulin and angiotensin II actions. At the extracellular level the angiotensin converting enzyme (ACE) regulates the synthesis of angiotensin II and bradykinin that is a powerful vasodilator. At early intracellular level angiotensin II acts on JAK-2/IRS1-IRS2/PI3-kinase, JNK and ERK to phosphorylate serine residues of key elements of insulin signaling pathway therefore inhibiting signaling by the insulin receptor. On another level angiotensin II inhibits the insulin signaling inducing the regulatory protein SOCS 3. Angiotensin II acting through the AT1 receptor can inhibit insulininduced nitric oxide (NO) production by activating ERK 1/2 and JNK and enhances the activity of NADPH oxidase that leads to an increased reactive oxygen species generation. From the clinical standpoint, the inhibition of the renin angiotensin system improves insulin sensitivity and decreases the incidence of Type 2 Diabetes Mellitus (T2DM). This might represent an alternative approach to prevent type 2 diabetes in patients with hypertension and metabolic syndrome, (i.e. insulin resistant patients). This review will discuss: a) the molecular mechanisms of the crosstalk between the insulin and angiotensin II signaling systems b) the results of clinical studies employing drugs targeting the renin-angiotensin IIaldosterone systems and their role in glucose metabolism and diabetes prevention.
Keywords: Insulin, Renin-Angiotensin-Aldosterone, Glucose Metabolism, Diabetes, hypertension, angiotensin converting enzyme (ACE), renin-angiotensin Iialdosterone systems
Current Vascular Pharmacology
Title: The Crosstalk Between Insulin and Renin-Angiotensin-Aldosterone Signaling Systems and its Effect on Glucose Metabolism and Diabetes Prevention
Volume: 6 Issue: 4
Author(s): Giovanna Muscogiuri, Alberto O. Chavez, Amalia Gastaldelli, Lucia Perego, Devjit Tripathy, Mario J. Saad, Licio Velloso and Franco Folli
Affiliation:
Keywords: Insulin, Renin-Angiotensin-Aldosterone, Glucose Metabolism, Diabetes, hypertension, angiotensin converting enzyme (ACE), renin-angiotensin Iialdosterone systems
Abstract: Essential hypertension is an insulin resistant state. Early insulin signaling steps are impaired in essential hypertension and a large body of data suggests that there is a crosstalk at multiple levels between the signal transduction pathways that mediate insulin and angiotensin II actions. At the extracellular level the angiotensin converting enzyme (ACE) regulates the synthesis of angiotensin II and bradykinin that is a powerful vasodilator. At early intracellular level angiotensin II acts on JAK-2/IRS1-IRS2/PI3-kinase, JNK and ERK to phosphorylate serine residues of key elements of insulin signaling pathway therefore inhibiting signaling by the insulin receptor. On another level angiotensin II inhibits the insulin signaling inducing the regulatory protein SOCS 3. Angiotensin II acting through the AT1 receptor can inhibit insulininduced nitric oxide (NO) production by activating ERK 1/2 and JNK and enhances the activity of NADPH oxidase that leads to an increased reactive oxygen species generation. From the clinical standpoint, the inhibition of the renin angiotensin system improves insulin sensitivity and decreases the incidence of Type 2 Diabetes Mellitus (T2DM). This might represent an alternative approach to prevent type 2 diabetes in patients with hypertension and metabolic syndrome, (i.e. insulin resistant patients). This review will discuss: a) the molecular mechanisms of the crosstalk between the insulin and angiotensin II signaling systems b) the results of clinical studies employing drugs targeting the renin-angiotensin IIaldosterone systems and their role in glucose metabolism and diabetes prevention.
Export Options
About this article
Cite this article as:
Muscogiuri Giovanna, Chavez O. Alberto, Gastaldelli Amalia, Perego Lucia, Tripathy Devjit, Saad J. Mario, Velloso Licio and Folli Franco, The Crosstalk Between Insulin and Renin-Angiotensin-Aldosterone Signaling Systems and its Effect on Glucose Metabolism and Diabetes Prevention, Current Vascular Pharmacology 2008; 6 (4) . https://dx.doi.org/10.2174/157016108785909715
DOI https://dx.doi.org/10.2174/157016108785909715 |
Print ISSN 1570-1611 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6212 |
Call for Papers in Thematic Issues
Ischemic Cardiovascular Diseases: Mechanisms, Diagnosis and Therapy
Ischemic cardiovascular disease includes myocardial infarction, coronary atherosclerotic heart disease, angina pectoris, etc., constitute the leading cause of patient mortality by preventing tissues from getting sufficient oxygen and nutrients. Ischemic heart disease, as a clinical condition, is characterized by myocardial ischemia, causing an imbalance between myocardial blood supply and demand, ...read more
TREATMENT OF CARDIOVASCULAR DISEASE IN CHRONIC AND END STAGE KIDNEY DISEASE
Cardiovascular disease still remains the leading cause of death in Chronic and End Stage Kidney Disease, accounting for more than half of all deaths in dialysis patients. During the past decade, research has been focused on novel therapeutic agents that might delay or even reverse cardiovascular disease and vascular calcification, ...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
-
Recent Patents on Diacylglycerol Production and Applications
Recent Patents on Chemical Engineering Preface
Current Cardiology Reviews Pediatric Chronic Daily Headache
Current Pediatric Reviews Detection of Myocardial Ischemia in Patients with Blunted Hemodynamic Response to Adenosine Stress
Current Medical Imaging Effect of Intranasal Administration of Galanin-like Peptide (GALP) on Body Weight and Hepatic Lipids Accumulation in Mice with Diet-induced Obesity
Current Pharmaceutical Design Regulation of the Activity of the Human Drug Metabolizing Enzyme Arylamine N-Acetyltransferase 1: Role of Genetic and Non Genetic Factors
Current Pharmaceutical Design Predementia and Dementia Syndromes: Possible Role of Lipoprotein Metabolism
Vascular Disease Prevention (Discontinued) Effects of Quercetin against Mycotoxin Induced Cytotoxicity: A Mini- Review
Current Nutrition & Food Science Novel Oral Anticoagulants in the Management of Polycythemia Vera and Essential Thrombocythemia
Cardiovascular & Hematological Agents in Medicinal Chemistry The Etiology of Hypertension in the Metabolic Syndrome Part Four: The Systemic Perspective – The Role of the Neuroendocrine and Immune Systems,and the Challenge of Integration
Current Vascular Pharmacology RAS Inhibition Attenuates Cognitive Impairment by Reducing Blood- Brain Barrier Permeability in Hypertensive Subjects
Current Hypertension Reviews Neurodevelopmental Delay and Intellectual Disability in Pediatric Heart Transplant
Current Psychiatry Reviews EDITORIAL (Hot Topic: Beyond Reproductive Effects of Sex Steroids)
Mini-Reviews in Medicinal Chemistry Detection and Treatment of Alcohol-Induced Hypertension
Current Hypertension Reviews Innovative Strategy in Treating Angina Pectoris with Chinese Patent Medicines by Promoting Blood Circulation and Removing Blood Stasis: Experience from Combination Therapy in Chinese Medicine
Current Vascular Pharmacology Patent Perspective for Potential Antioxidant Compounds-Rutin and Quercetin
Recent Patents on Nanomedicine Editorial [Hot Topic: Metabolic Syndrome in an Asian Chinese Population and Agents and Targets for Cardiovascular Protection (Guest Editors: M.L. Fung and T.M. Wong)]
Cardiovascular & Hematological Disorders-Drug Targets Pharmacotherapy for Obesity
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Apoptogenic Signal Transduction in Arteriosclerosis-Associated Cells – Opportunities for Future Therapy?
Vascular Disease Prevention (Discontinued) Determinants of Perceived Severity of Hypertension and Drug-Compliance in Hypertensive Patients
Cardiovascular & Hematological Disorders-Drug Targets