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In medicine and pharmacology, pioglitazone is a member of the drug class of the thiazolidinediones.
It is being marketed as Actos® by the pharmaceutical companies Takeda and Eli Lilly.
Like other thiazolidinediones, its mechanism of action is by activation the intracellular receptor class of the peroxisome proliferator-activated receptors (PPARs), specifically PPARγ.
Mode of action
Thiazolidinediones act by binding to PPARs (peroxisome proliferator-activated receptors), a group of receptor molecules inside the cell nucleus, specifically PPARγ (gamma). The normal ligands for these receptors are free fatty acids (FFAs) and eicosanoids. When activated, the receptor migrates to the DNA, activating transcription of a number of specific genes.
Genes upregulated by PPARγ can be found in the main article on peroxisome proliferator-activated receptors.
By activating PPARγ:
insulin resistance is decreased
adipocyte differentiation is modified
VEGF-induced angiogenesis is inhibited (abstract).
Leptin levels decrease (leading to an increased appetite)
Levels of certain interleukins (e.g. IL-6) fall
Adiponectin levels rise
Members of the class
Troglitazone was withdrawn from the market due to an increased incidence of drug-induced hepatitis in patients who were using the drug. It is now common practice that liver enzymes are monitored during the first year of treatment with the "newer" thiazolidinediones.
Experimental agents include MCC-555, a powerful antidiabetic agent and the early non-marketed thiazolidinedione ciglitazone.
The only registered use of the thiazolidinediones is in diabetes mellitus type 2.
It is being investigated experimentally in polycystic ovary syndrome (PCOS) and non-alcoholic steatohepatitis (NASH).
Several forms of lipodystrophy cause insulin resistance, which has responded favorably to thiazolidinediones.
Side-effects and contraindications
The withdrawal of troglitazone has led to concerns of other thiazolidinediones increasing the risk of hepatitis. Guidelines now mention that for the first year of thiazolidinedione therapy, a two- or three-monthly check of liver enzymes is conducted to ascertain that no liver damage is occurring.
The main side-effect of all thiazolidinediones is fluid retention, leading to edema and potentially aggravating heart failure. Therefore, thiazolidinediones cannot be prescribed in patients with decreased ventricular function (NYHA grade III and IV heart failure).
Retrieved from "http://en.wikipedia.org/wiki/Thiazolidinedione"
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