TY - JOUR
T1 - Transcriptional Co-activator p300 maintains basal hepatic gluconeogenesis
AU - He, Ling
AU - Naik, Karuna
AU - Meng, Shumei
AU - Cao, Jia
AU - Sidhaye, Aniket R.
AU - Ma, Anlin
AU - Radovick, Sally
AU - Wondisford, Fredric E.
PY - 2012/9/14
Y1 - 2012/9/14
N2 - A major cause of fasting hyperglycemia in diabetes mellitus is unregulated hepatic glucose production (HGP). Insulin suppresses HGP by phosphorylating CBP and disassembling the CREB-CBP complex from gluconeogenic genes. p300 is closely related to CBP; but in contrast to CBP, p300 binds constitutively to CREB due to the absence of phosphorylation site found in CBP. In a phosphorylation- competent p300(G442S) knock-in mouse model, we demonstrate that HGP is now exquisitely sensitive to insulin suppression. p300(G422S) and hepatic-deleted p300 mice exhibited significant lower blood glucose levels in the fasted and post-prandial states, indicating a role for p300 in maintaining basal HGP.
AB - A major cause of fasting hyperglycemia in diabetes mellitus is unregulated hepatic glucose production (HGP). Insulin suppresses HGP by phosphorylating CBP and disassembling the CREB-CBP complex from gluconeogenic genes. p300 is closely related to CBP; but in contrast to CBP, p300 binds constitutively to CREB due to the absence of phosphorylation site found in CBP. In a phosphorylation- competent p300(G442S) knock-in mouse model, we demonstrate that HGP is now exquisitely sensitive to insulin suppression. p300(G422S) and hepatic-deleted p300 mice exhibited significant lower blood glucose levels in the fasted and post-prandial states, indicating a role for p300 in maintaining basal HGP.
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U2 - 10.1074/jbc.M112.385864
DO - 10.1074/jbc.M112.385864
M3 - Article
C2 - 22815486
AN - SCOPUS:84866415671
SN - 0021-9258
VL - 287
SP - 32069
EP - 32077
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 38
ER -