title: Transcriptional co-activator p300 maintains basal hepatic gluconeogenesis.
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.
authors: Division of Metabolism, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA. heling@jhmi.ed
authors: Ling
authors: L
authors: He
authors: Karuna
authors: K
authors: Naik
authors: Shumei
authors: S
authors: Meng
authors: Jia
authors: J
authors: Cao
authors: Aniket R
authors: AR
authors: Sidhaye
authors: Anlin
authors: A
authors: Ma
authors: Sally
authors: S
authors: Radovick
authors: Fredric E
authors: FE
authors: Wondisford
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005786:Gene Expression Regulation; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D022781:Hepatocytes / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D050880:p300-CBP Transcription Factors / Q000378:metabolism*
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D050880:p300-CBP Transcription Factors; D005947:Glucose