Transcriptional Co-activator p300 maintains basal hepatic gluconeogenesis

Ling He, Karuna Naik, Shumei Meng, Jia Cao, Aniket R. Sidhaye, Anlin Ma, Sally Radovick, Fredric E. Wondisford

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)32069-32077
Number of pages9
JournalJournal of Biological Chemistry
Volume287
Issue number38
DOIs
StatePublished - Sep 14 2012

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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