Peroxisome proliferatoractivator receptor gamma PPARg

Peroxisome proliferator-activated receptors (PPARs) are orphan receptors belonging to the steroids/thyroid/retinoid receptor super family of ligand-activated transcription factors. There are three PPAR isoforms (PPARa, -p, -g), each of which is differentially expressed and displays a distinct pattern of ligand specificity [50]. PPARs are implicated in several physiological processes, such as the regulation of lipoprotein, lipid metabolism and glucose homeostasis. Recent observations indicate that PPAR activators could reduce the inflammation induced in different inflammatory pathologies including asthma, hypertensive heart disease, hepatic inflammation and cerebral ischemia [51]. In vivo, PPARg agonists have been shown to modulate inflammatory responses in the brain and to reduce infract size following transient focal ischemia [52,53]. Cerebral ischemia is frequently accompanied by inflammation, which can worsen neuronal injury [54]. Activation of PPARg reduces inflammation and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase [55]. In addition, PPARg activators increase levels of CuZn-superoxide dismutase (SOD) in cultured endothelium, suggesting an additional mechanism by which it may exert protective effects within the brain [56]. To date, a large number of structurally diverse synthetic ligands have been discovered which modulate PPARg activity. The first compounds reported as high-affinity PPAR agonists are a class of compounds known as 'glitazones' or thiazolidinediones (TZDs). Initial compounds in this class, Troglitazone (19), Pioglitazone (20), Rosiglitazone (21), were subtype selective, high-affinity agonists for PPARg [54,57,58]. Troglitazone was the first drug to be approved for treating type 2 diabetes, but was withdrawn from the market in 1999 due to hepatic toxicity. However, Pioglitazone and Rosiglitazone are now available and reportedly show no hepatic side effects [52,59,60]. The latter two drugs in this class were shown to exert protective effects against cerebral ischemia/reper-fusion injury by reducing oxidative stress and inflammatory response. Both drugs were administered 30 min prior to ischemia and the rapid onset of their protective effects might suggest a potential role of PPARg agonist in modulating the early events occurring during transitory ischemic attacks [56,61,62].

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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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