The medication class of thiazolidinedione was introduced in the late 1990s as an adjunctive therapy for diabetes mellitus (type II) and related diseases. A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... The 1990s decade refers to the years from 1990 to 1999, inclusive, the last decade of the 20th Century. ... For the disease characterized by excretion of large amounts of severely diluted urine, see diabetes insipidus. ...

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. PPAR gamma In cell biology, peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor isoforms that exist across biology. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... In cell biology, the nucleus (from Latin nucleus or nuculeus, kernel) is found in all eukaryotic cells and contains most of the cells genetic material. ... It has been suggested that this article or section be merged with Ligand (biochemistry). ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid (or organic acid), often with a long aliphatic tail (long chains), either saturated or unsaturated. ... In biochemistry, eicosanoids are a class of oxygenated hydrophobic cytokines that largely function as a autocrine and paracrine mediators. ... The general structure of a section of DNA Deoxyribonucleic acid (DNA) is a nucleic acid —usually in the form of a double helix— that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). ... Transcription may be one of the following: In linguistics, transcription is the conversion of spoken words into written language. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ...

Genes upregulated by PPARγ can be found in the main article on peroxisome proliferator-activated receptors. PPAR gamma In cell biology, peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor isoforms that exist across biology. ...

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

In medicine, insulin resistance denotes a decompensation of glucose homeostasis where the tissues appear to be less responsive to insulin. ... Adipocytes are cells present in adipose tissue, specialized in storing energy as fat. ... Vascular endothelial growth factor or VEGF is an important signal protein involved in angiogenesis. ... Angiogenesis is the physiological process involving the formation of new blood vessels from pre-existing vessels. ... Leptin is a 16 kDa protein hormone that plays a key role in metabolism and regulation of adipose tissue. ... The appetite is the desire to eat food, felt as hunger. ... Interleukins are a group of cytokines that are expressed by white blood cells (leukocytes, hence the -leukin) as a means of communication (inter-). The function of the immune system depends in a large part on interleukins, and rare deficiencies of a number of them have been described, all featuring autoimmune...

Members of the class

These include:

• rosiglitazone
• pioglitazone

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. Rosiglitazone is an anti-diabetic drug from the thiazolidinedione class. ... In medicine and pharmacology, pioglitazone is a member of the drug class of the thiazolidinediones. ... Troglitazone (Rezulin®, Resulin® or Romozin®) is a member of the drug class of the thiazolidinediones. ... Hepatitis is a gastroenterological disease, featuring inflammation of the liver. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ...

Experimental agents include MCC-555, a powerful antidiabetic agent and the early non-marketed thiazolidinedione ciglitazone. An anti-diabetic drug or oral hypoglycemic agent is used to treat diabetes mellitus. ...

Uses

The only registered use of the thiazolidinediones is in diabetes mellitus type 2. For the disease characterized by excretion of large amounts of severely diluted urine, see diabetes insipidus. ...

It is being investigated experimentally in polycystic ovary syndrome (PCOS) and non-alcoholic steatohepatitis (NASH). Polycystic Ovary by Sonography Polycystic ovary syndrome (PCOS, also known clinically as Stein-Leventhal syndrome), is an endocrine disorder that affects 5–10% of women. ... As its name signifies, Non-alcoholic steatohepatitis (NASH) or Nonalcoholic Fatty Liver Disease (NAFLD) is fatty inflammation of the liver when this is not due to excessive alcohol use. ...

Several forms of lipodystrophy cause insulin resistance, which has responded favorably to thiazolidinediones. In medicine, lipodystrophy is a condition characterized by abnormal or degernative conditions of the bodys fat tissue. ...

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. Troglitazone (Rezulin®, Resulin® or Romozin®) is a member of the drug class of the thiazolidinediones. ... Hepatitis is a gastroenterological disease, featuring inflammation of the liver. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ...

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). Edema (BE: oedema, formerly known as dropsy) is swelling of any organ or tissue due to accumulation of excess fluid. ... The New York Heart Association (NYHA) Functional Classification provides a simple way of classifying the extent of heart failure. ...