Transcriptional activation of SHP by PPAR-gamma in liver.
The mechanism of how PPARgamma decrease gluconeogenic gene expressions in liver is still unclear. Since PPARgamma is a transcriptional activator, it requires a mediator to decrease the transcription of gluconeogenic genes. Recently, SHP has been shown to mediate the bile acid-dependent down regulation of gluconeogenic gene expression in liver. This led us to explore the possibility that SHP may mediate the antigluconeogenic effect of PPARgamma. In the present study, we have identified and characterized the presence of functional PPRE in human SHP promoter. We show the binding of PPARgamma/RXRalpha heterodimer to the PPRE and increased SHP expression by rosiglitazone in primary rat hepatocytes. Taken together with the previous reports about the function of SHP on gluconeogenesis, our results indicate that SHP can mediate the acute antigluconeogenic effect of PPARgamma.
Kim
Ha-il
HI
Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Republic of Korea.
Koh
Yoo-Kyung
YK
Kim
Tae-Hyun
TH
Kwon
Sool-Ki
SK
Im
Seung-Soon
SS
Choi
Hueng-Sik
HS
Kim
Kyung-Sup
KS
Ahn
Yong-Ho
YH
D000818:Animals; D002478:Cells, Cultured; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation / Q000502:physiology*
D047495:PPAR gamma; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509250:Ptpn6 protein, rat