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 language | English (US) |
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Pages (from-to) | 32069-32077 |
Number of pages | 9 |
Journal | Journal of Biological Chemistry |
Volume | 287 |
Issue number | 38 |
DOIs | |
State | Published - Sep 14 2012 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology