Transcriptional Co-activator p300 Maintains Basal Hepatic Gluconeogenesis

被引:43
作者
He, Ling [1 ,2 ,3 ]
Naik, Karuna
Meng, Shumei [1 ,2 ,3 ]
Cao, Jia [1 ,2 ,3 ]
Sidhaye, Aniket R. [1 ,2 ,3 ]
Ma, Anlin [1 ,2 ,3 ]
Radovick, Sally [4 ,5 ,6 ,7 ]
Wondisford, Fredric E. [1 ,2 ,3 ]
机构
[1] Johns Hopkins Univ, Sch Med, Div Metab, Dept Pediat, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Sch Med, Div Metab, Dept Physiol, Baltimore, MD 21287 USA
[3] Johns Hopkins Univ, Sch Med, Div Metab, Dept Med, Baltimore, MD 21287 USA
[4] Johns Hopkins Univ, Sch Med, Div Endocrinol, Dept Pediat, Baltimore, MD 21287 USA
[5] Johns Hopkins Univ, Sch Med, Div Endocrinol, Dept Physiol, Baltimore, MD 21287 USA
[6] Johns Hopkins Univ, Sch Med, Div Endocrinol, Dept Med, Baltimore, MD 21287 USA
[7] Univ Chicago, Dept Med, Chicago, IL 60637 USA
基金
美国国家卫生研究院;
关键词
CREB-BINDING-PROTEIN; GLUCOSE-PRODUCTION; SREBP FAMILY; PHOSPHORYLATION; CBP; ACETYLATION; KINASE; MICE; GLYCOGENOLYSIS; SUPPRESSION;
D O I
10.1074/jbc.M112.385864
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:32069 / 32077
页数:9
相关论文
共 29 条
[1]   Higher insulin concentrations are required to suppress gluconeogenesis than glycogenolysis in nondiabetic humans [J].
Adkins, A ;
Basu, R ;
Persson, M ;
Dicke, B ;
Shah, P ;
Vella, A ;
Schwenk, WF ;
Rizza, R .
DIABETES, 2003, 52 (09) :2213-2220
[2]   E1A-ASSOCIATED P300 AND CREB-ASSOCIATED CBP BELONG TO A CONSERVED FAMILY OF COACTIVATORS [J].
ARANY, Z ;
SELLERS, WR ;
LIVINGSTON, DM ;
ECKNER, R .
CELL, 1994, 77 (06) :799-800
[3]   Disrupting the CH1 Domain Structure in the Acetyltransferases CBP and p300 Results in Lean Mice with Increased Metabolic Control [J].
Bedford, David C. ;
Kasper, Lawryn H. ;
Wang, Ruoning ;
Chang, Yunchao ;
Green, Douglas R. ;
Brindle, Paul K. .
CELL METABOLISM, 2011, 14 (02) :219-230
[4]   Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD) [J].
Bellentani, Stefano ;
Marino, Mariano .
ANNALS OF HEPATOLOGY, 2009, 8 :S4-S8
[5]   FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis [J].
Boden, G ;
Cheung, P ;
Stein, TP ;
Kresge, K ;
Mozzoli, M .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2002, 283 (01) :E12-E19
[6]   Salt-inducible kinase 2 links transcriptional coactivator p300 phosphorylation to the prevention of ChREBP-dependent hepatic steatosis in mice [J].
Bricambert, Julien ;
Miranda, Jonatan ;
Benhamed, Fadila ;
Postic, Jean Girard Catherine ;
Dentin, Renaud .
JOURNAL OF CLINICAL INVESTIGATION, 2010, 120 (12) :4316-4331
[7]  
Chan HM, 2001, J CELL SCI, V114, P2363
[8]   Interaction of the TAZ1 domain of the CREB-binding protein with the activation domain of CITED2 - Regulation by competition between intrinsically unstructured ligands for non-identical binding sites [J].
De Guzman, RN ;
Martinez-Yamout, MA ;
Dyson, HJ ;
Wright, PE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (04) :3042-3049
[9]   Association of hypoglycemia and cardiac ischemia - A study based on continuous monitoring [J].
Desouza, C ;
Salazar, H ;
Cheong, B ;
Murgo, J ;
Fonseca, V .
DIABETES CARE, 2003, 26 (05) :1485-1489
[10]   Prevention of diabetic retinopathy [J].
Einarsdottir, Ann B. ;
Stefansson, Einar .
LANCET, 2009, 373 (9672) :1316-1318