Insulin resistance and PPAR insulin sensitizers.
Drugs that reverse insulin resistance are of importance as insulin resistance is frequently associated with type 2 diabetes. The three peroxisome proliferator-activated receptors (PPARs) PPARalpha, PPAR90 and PPARgamma are essential for the actions of the many insulin sensitizers. PPARalpha activation enhances free fatty acid oxidation and potentiates anti-inflammatory effects, while PPARgamma is essential for normal adipocyte differentiation and proliferation, as well as fatty acid uptake and storage. Thiazolidinediones (TZDs) are selective ligands of PPARgamma and act as insulin sensitizers. TZDs also suppress free fatty acids via the inhibition of lipolysis in adipose tissue. Insulin sensitizers currently under development include partial PPARgamma agonists and antagonists, and dual PPARalpha/PPARgamma agonists. Given that TZDs show anti-inflammatory, anti-oxidant and antiprocoagulant properties in addition to their insulin sensitizing and antilipotoxic properties, a case may be made for initiating TZD therapy early in the treatment of type 2 diabetes, particularly in those patients at risk of cardiovascular disease. TZDs may also be an important therapeutic option in the treatment of metabolic syndrome.
Bhatia
Vishal
V
State University of New York, Department of Diabetes, Endocrinology and Metabolism, Buffalo, NY 14209, USA. vbhatia@buffalo.edu
Viswanathan
Prabhakar
P
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology*; D008055:Lipids / Q000097:blood; D047492:Peroxisome Proliferator-Activated Receptors / Q000502:physiology*; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D008055:Lipids; D047492:Peroxisome Proliferator-Activated Receptors; D045162:Thiazolidinediones