Thiazolidinediones in the treatment of insulin resistance and type II diabetes

• Published in: Diabetes (New York, N.Y.) Vol. 45; no. 12; pp. 1661 - 1669
• Main Authors: Saltiel, A. R., Olefsky, J. M.
• Format: Journal Article
• Language: English
• Published: American Diabetes Association 01-12-1996
• ISSN: 0012-1797; 1939-327X; 0012-1797
• DOI: 10.2337/diabetes.45.12.1661

Thiazolidinediones in the treatment of insulin resistance and type II diabetes.
A R Saltiel and
J M Olefsky
Department of Signal Transduction, Parke-Davis Pharmaceutical Research Division, Warner Lambert, Ann Arbor, Michigan, USA.
Abstract
Insulin resistance, characterized by reduced responsiveness to normal circulating concentrations of insulin, is a common feature
of almost all patients with type II diabetes. The presumed central roles of both peripheral and hepatic insulin resistance
suggest that the enhancement of insulin action might be an effective pharmacological approach to diabetes. Thiazolidinediones
are a new class of orally active drugs that are designed to enhance the actions of insulin. These agents reduce insulin resistance
by increasing insulin-dependent glucose disposal and reducing hepatic glucose output. Clinical studies in patients with type
II diabetes, as well as other syndromes characterized by insulin resistance, have demonstrated that thiazolidinediones may
represent a safe and effective new treatment. Although the precise mechanism of action of these drugs remains unknown, transcriptional
changes are observed in tissue culture cells that produce enhanced insulin action. This regulation of gene expression appears
to be mediated by the interactions of thiazolidinediones with a family of nuclear receptors known as the peroxisome proliferator-activated
receptors (PPARs). The further elucidation of the molecular actions of these drugs may reveal much about the underlying mechanisms
of insulin resistance.