Thiazolidinediones: effects on insulin resistance and the cardiovascular system

• Published in: British journal of pharmacology Vol. 153; no. 4; pp. 636 - 645
• Main Authors: Quinn, C E, Hamilton, P K, Lockhart, C J, McVeigh, G E
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2008; Nature Publishing; Nature Publishing Group
• Subjects: Adipokines - metabolism; adiponectin; adipose; Animals; atherosclerosis; Atherosclerosis (general aspects, experimental research); Atherosclerosis - complications; Atherosclerosis - metabolism; Atherosclerosis - physiopathology; Atherosclerosis - prevention & control; Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; cardiovascular; Cardiovascular Diseases - etiology; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - physiopathology; Cardiovascular Diseases - prevention & control; Cardiovascular System - drug effects; Cardiovascular System - metabolism; Cardiovascular System - physiopathology; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; glucose; Humans; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; inflammation; Insulin Resistance; Medical sciences; peroxisome proliferator‐activated receptor‐γ; Pharmacology. Drug treatments; PPAR alpha - agonists; PPAR alpha - metabolism; PPAR gamma - agonists; PPAR gamma - metabolism; Reviews; Risk Assessment; Risk Factors; thiazolidinedione; Thiazolidinediones - adverse effects; Thiazolidinediones - therapeutic use; Treatment Outcome; Endocrinopathy; Pancreatic hormone; peroxisome proliferator-activated receptor-y; thiazolidinedione; Adipose tissue; Cardiovascular disease; Thiazolidinedione derivatives; Inflammation; adipose; Glucose; cardiovascular; Insulin; Adiponectin; Vascular disease; Target tissue resistance; Atherosclerosis; Circulatory system; insulin resistance; Peroxisome proliferator activated receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0707452

Thiazolidinediones (TZDs) have been used for the treatment of hyperglycaemia in type 2 diabetes for the past 10 years. They may delay the development of type 2 diabetes in individuals at high risk of developing the condition, and have been shown to have potentially beneficial effects on cardiovascular risk factors. TZDs act as agonists of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) primarily in adipose tissue. PPAR‐γ receptor activation by TZDs improves insulin sensitivity by promoting fatty acid uptake into adipose tissue, increasing production of adiponectin and reducing levels of inflammatory mediators such as tumour necrosis factor‐alpha (TNF‐α), plasminogen activator inhibitor‐1(PAI‐1) and interleukin‐6 (IL‐6). Clinically, TZDs have been shown to reduce measures of atherosclerosis such as carotid intima‐media thickness (CIMT). However, in spite of beneficial effects on markers of cardiovascular risk, TZDs have not been definitively shown to reduce cardiovascular events in patients, and the safety of rosiglitazone in this respect has recently been called into question. Dual PPAR‐α/γ agonists may offer superior treatment of insulin resistance and cardioprotection, but their safety has not yet been assured. British Journal of Pharmacology (2008) 153, 636–645; doi:10.1038/sj.bjp.0707452; published online 1 October 2007