Thiazolidinediones

The thiazolidinediones (TZDs) also known as glitazones, are a class of medications used in the treatment of diabetes mellitus type 2. They were introduced in the late 1990s.

Thiazolidinediones act as insulin sensitizers in a cell. They work by binding to the peroxisome proliferator-activated receptors (PPARs). PPARs are receptors on the membrane of the cell nucleus. Thiazolidinediones enter the cell, bind to the nuclear receptors, and affect the expression of DNA. There are several PPARs, including PPARα (alpha), PPARβ/δ (beta/delta), and PPARγ (gamma). Thiazolidinediones bind to PPARγ (gamma). By activating PPARγ (gamma).:

• Insulin resistance is decreased

• Adipocyte differentiation is modified

• VEGF-induced angiogenesis is inhibited

• Leptin levels decrease (leading to an increased appetite)

• Levels of certain interleukins (e.g. IL-6) fall

• Adiponectin levels rise

PPARs are found in fat cells, cells of the liver, muscle, heart, and inner wall (endothelium) and smooth muscle of blood vessels. PPARγ (gamma) is expressed mainly in fat tissue, where it regulates genes involved in fat cell (adipocyte) differentiation, fatty acid uptake and storage, and glucose uptake. It is also found in pancreatic beta cells, vascular endothelium, and macrophages.

This class of drugs has not been without its problems and few are left on the market. Chemically, the members of this class are derivatives of the parent compound thiazolidinedione.