Reactome | PPARG binds PPARG agonists

PPARG binds PPARG agonists

Stable Identifier

R-HSA-9732629

Type

Reaction [binding]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Peroxisome proliferator-activated receptor gamma (PPARG) is expressed mainly in fat tissue, where it regulates genes involved in fat cell (adipocyte) differentiation, fatty acid uptake and storage, and glucose uptake. PPARG is a nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, PPARG binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes. PPARG can regulate peroxisomal fatty acid beta-oxidation, adipocyte differentiation and glucose homeostasis.

Thiazolidinediones (TZDs, glitazones) are a family of drugs acting as insulin sensitizers and are only approved for the treatment of type 2 diabetes mellitus (T2DM). TZDs are PPARG agonists and act via PPARG to make cells more responsive to insulin. TZDs used to manage T2DM are rosiglitazone (Henke et al. 1998, Young et al. 1998), pioglitazone (Sakamoto et al. 2000) and troglitazone (Henke et al. 1998). Troglitazone was withdrawn in 2000 due to risk of hepatotoxicity (Graham et al. 2001) but has since been extensively studied using a variety of in vivo, in vitro and computational methods (Kassahun et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
9836620	N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents Collins, JL, Brackeen, MF, Kliewer, SA, Lehmann, JM, Blanchard, SG, Brown, KK, Leesnitzer, LM, Henke, BR, Hull-Ryde, EA, Miller, JF, Kaldor, I, Willson, TM, Szewczyk, JR, Orband-Miller, LA, Cobb, JE, Harrington, WW, Oliver, W, Mook, RA, Plunket, KD, Noble, SA, Lenhard, JM, Parks, DJ, Lake, DH, Hashim, MA	J Med Chem	1998
9454824	Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor gamma Chapman, H, Kallender, H, Coyle, PJ, Murphy, GJ, Clapham, JC, Hindley, RM, Cantello, BC, Mossakowska, D, Young, PW, Holder, JC, Buckle, DR, Lawrie, KW, Roxbee Cox, L, Latter, AJ, Haigh, D, Smith, SA	J Pharmacol Exp Ther	1998
11095972	Activation of human peroxisome proliferator-activated receptor (PPAR) subtypes by pioglitazone Odaka, H, Sawada, H, Moriyama, S, Sugiyama, Y, Momose, Y, Kimura, H, Sakamoto, J	Biochem Biophys Res Commun	2000