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p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis.

Publication ,  Journal Article
Cao, W; Collins, QF; Becker, TC; Robidoux, J; Lupo, EG; Xiong, Y; Daniel, KW; Floering, L; Collins, S
Published in: J Biol Chem
December 30, 2005

Hepatic gluconeogenesis is essential for maintaining blood glucose levels during fasting and is the major contributor to postprandial and fasting hyperglycemia in diabetes. Gluconeogenesis is a classic cAMP/protein kinase A-dependent process initiated by glucagon, which is elevated in the blood during fasting and in diabetes. In this study, we have shown that p38 mitogen-activated protein kinase (p38) was activated in liver by fasting and in primary hepatocytes by glucagon or forskolin. Fasting plasma glucose levels were reduced upon blockade of p38 with either a chemical inhibitor or small interference RNA in mice. In examining the mechanism, inhibition of p38 suppressed gluconeogenesis in liver, along with expression of key gluconeogenic genes, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Peroxisome proliferator-activated receptor gamma coactivator 1alpha and cAMP-response element-binding protein have been shown to be important mediators of hepatic gluconeogenesis. We have shown that inhibition of p38 prevented transcription of the PPARgamma coactivator 1alpha gene as well as phosphorylation of cAMP-response element-binding protein. Together, our results from in vitro and in vivo studies define a model in which cAMP-dependent activation of genes involved in gluconeogenesis is dependent upon the p38 pathway, thus adding a new player to our evolving understanding of this physiology.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 30, 2005

Volume

280

Issue

52

Start / End Page

42731 / 42737

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transfection
  • Transcription Factors
  • Trans-Activators
  • Streptozocin
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Pyridines
  • Promoter Regions, Genetic
  • Phosphorylation
 

Citation

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Cao, W., Collins, Q. F., Becker, T. C., Robidoux, J., Lupo, E. G., Xiong, Y., … Collins, S. (2005). p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J Biol Chem, 280(52), 42731–42737. https://doi.org/10.1074/jbc.M506223200
Cao, Wenhong, Qu Fan Collins, Thomas C. Becker, Jacques Robidoux, Edgar G. Lupo, Yan Xiong, Kiefer W. Daniel, Lisa Floering, and Sheila Collins. “p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis.J Biol Chem 280, no. 52 (December 30, 2005): 42731–37. https://doi.org/10.1074/jbc.M506223200.
Cao W, Collins QF, Becker TC, Robidoux J, Lupo EG, Xiong Y, et al. p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J Biol Chem. 2005 Dec 30;280(52):42731–7.
Cao, Wenhong, et al. “p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis.J Biol Chem, vol. 280, no. 52, Dec. 2005, pp. 42731–37. Pubmed, doi:10.1074/jbc.M506223200.
Cao W, Collins QF, Becker TC, Robidoux J, Lupo EG, Xiong Y, Daniel KW, Floering L, Collins S. p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J Biol Chem. 2005 Dec 30;280(52):42731–42737.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

December 30, 2005

Volume

280

Issue

52

Start / End Page

42731 / 42737

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Transfection
  • Transcription Factors
  • Trans-Activators
  • Streptozocin
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Pyridines
  • Promoter Regions, Genetic
  • Phosphorylation