Insulin inhibits hepatocellular glucose production by utilizing liver-enriched transcriptional inhibitory protein to disrupt the association of CREB-binding protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene promoter

David T Duong; Mary E Waltner-Law; Rosalie Sears; Linda Sealy; Daryl K Granner

doi:10.1074/jbc.M204873200

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Insulin inhibits hepatocellular glucose production by utilizing liver-enriched transcriptional inhibitory protein to disrupt the association of CREB-binding protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene promoter

Journal article

Open access

Peer reviewed

Insulin inhibits hepatocellular glucose production by utilizing liver-enriched transcriptional inhibitory protein to disrupt the association of CREB-binding protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene promoter

David T Duong, Mary E Waltner-Law, Rosalie Sears, Linda Sealy and Daryl K Granner

The Journal of biological chemistry, Vol.277(35), pp.32234-32242

08/30/2002

DOI: 10.1074/jbc.M204873200

PMID: 12070172

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Abstract

Hormones regulate glucose homeostasis, in part, by controlling the expression of gluconeogenic enzymes, such as phosphoenolpyruvate carboxykinase (PEPCK). Insulin and glucocorticoids reciprocally regulate PEPCK expression primarily at the level of gene transcription. We demonstrate here that glucocorticoids promote, whereas insulin disrupts, the association of CREB-binding protein (CBP) and RNA polymerase II with the hepatic PEPCK gene promoter in vivo. We also show that accessory factors, such as CCAAT/enhancer-binding protein beta (C/EBP beta), can recruit CBP to drive transcription. Insulin increases protein levels of liver-enriched transcriptional inhibitory protein (LIP), an inhibitory form of C/EBP beta, in a phosphatidylinositol 3-kinase-dependent manner. LIP concomitantly replaces liver-enriched transcriptional activator protein on the PEPCK gene promoter, which can abrogate the recruitment of CBP and polymerase II, culminating in the repression of PEPCK expression and the attenuation of hepatocellular glucose production.

Transfection

Insulin - pharmacology

Promoter Regions, Genetic

Transcription, Genetic - drug effects

RNA Polymerase II - antagonists & inhibitors

RNA, Messenger - genetics

Rats

Glucose - antagonists & inhibitors

Recombinant Fusion Proteins - metabolism

CCAAT-Enhancer-Binding Protein-beta - metabolism

Phosphoenolpyruvate Carboxykinase (GTP) - genetics

Luciferases - genetics

Cyclic AMP - pharmacology

Animals

Chromatin - physiology

Cyclic AMP Response Element-Binding Protein - antagonists & inhibitors

Glucocorticoids - pharmacology

Glucose - metabolism

Kinetics

Tumor Cells, Cultured

Chromatin - drug effects

Liver Neoplasms, Experimental

Details

Title: Subtitle: Insulin inhibits hepatocellular glucose production by utilizing liver-enriched transcriptional inhibitory protein to disrupt the association of CREB-binding protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene promoter
Creators: David T Duong - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
Mary E Waltner-Law
Rosalie Sears
Linda Sealy
Daryl K Granner
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(35), pp.32234-32242
DOI: 10.1074/jbc.M204873200
PMID: 12070172
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: DK20593 / NIDDK NIH HHS GM07347 / NIGMS NIH HHS DK02887 / NIDDK NIH HHS DK35107 / NIDDK NIH HHS DK07061 / NIDDK NIH HHS
Language: English
Date published: 08/30/2002
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984020608102771

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