Peroxisome Proliferator Activated Receptory Key Regulator of Adipogenesis and Insulin Sensitivity

PPAR-y was first identified as a part of a transcriptional complex essential for the differentiation of adipocytes, a cell type in which PPAR-y is highly expressed and critically involved (6). Homozygous PPAR-y-deficient animals die at about day 10 in utero as a result of various abnormalities including cardiac malformations and absent white fat (7-9). PPAR-y is also involved in lipid metabolism, with target genes such as human menopausal gonadotropin coenzyme A synthetase and apolipoprotein (apo)-A-I (10,11). Chemical screening and subsequent studies led to the serendipitous discovery that thiazolidinediones (TZDs) were insulin sensitizers that lower glucose by binding to PPAR-y. Used clinically as antidiabetic agents, the TZD class includes pioglitazone (Actos) and rosiglitazone (formerly BRL49653, now Avandia) (12,13). Troglitazone (ReZulin) was withdrawn from the market because of idiosyncratic liver failure. Naturally occurring PPAR-y ligands have been proposed, although with more controversy, as discussed below. The fact that dominant negative mutations in PPAR-y have been associated with severe insulin resistance and hypertension provides another argument for the importance of these receptors in human biology (14,15).

Diabetes 2

Diabetes 2

Diabetes is a disease that affects the way your body uses food. Normally, your body converts sugars, starches and other foods into a form of sugar called glucose. Your body uses glucose for fuel. The cells receive the glucose through the bloodstream. They then use insulin a hormone made by the pancreas to absorb the glucose, convert it into energy, and either use it or store it for later use. Learn more...

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