The antidiabetic agent thiazolidinedione stimulates the interaction between PPAR gamma and CBP.
The peroxisome proliferator-activated receptor (PPAR) gamma is a member of the nuclear hormone receptor family, which is predominantly expressed on adipocytes and considered to be involved in the process of adipogenesis. The new thiazolidinedione (TZD) compound, T-174, developed as an antidiabetic drug, stimulated the transcription of PPAR gamma and the adipocyte differentiation of 3T3-L1 cells. Interestingly, T-174 induced the interaction between PPAR gamma and CBP (cAMP response element binding protein (CREB) binding protein), a co-factor of various transcription regulators. CBP mRNA was expressed in both preadipocytes and adipocytes. These results suggest that CBP plays a role in the PPAR gamma-mediated signaling pathway activated by TZD, including adipogenesis.
Mizukami
J
J
Lead Generation Research Laboratory, Tanabe Seiyaku Co., Ltd., Osaka, Japan. junko-m@tanabe.co.jp
Taniguchi
T
T
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002951:Citrates / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D051379:Mice; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology*; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism*
D002352:Carrier Proteins; D002951:Citrates; D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D014157:Transcription Factors; C020723:citrate-binding transport protein