CRTC2 (TORC2) Contributes to the Transcriptional Response to Fasting in the Liver but Is Not Required for the Maintenance of Glucose Homeostasis

John Le Lay, Geetu Tuteja, Peter White, Ravindra Dhir, Rexford Ahima, Klaus H. Kaestner

Research output: Contribution to journalArticle

Abstract

The liver contributes to glucose homeostasis by promoting either storage or production of glucose, depending on the physiological state. The cAMP response element-binding protein (CREB) is a principal regulator of genes involved in coordinating the hepatic response to fasting, but its mechanism of gene activation remains controversial. We derived CRTC2 (CREB-regulated transcription coactivator 2, previously TORC2)-deficient mice to assess the contribution of this cofactor to hepatic glucose metabolism in vivo. CRTC2 mutant hepatocytes showed reduced glucose production in response to glucagon, which correlated with decreased CREB binding to several gluconeogenic genes. However, despite attenuated expression of CREB target genes, including PEPCK, G6Pase, and PGC-1α, no hypoglycemia was observed in mutant mice. Collectively, these results provide genetic evidence supporting a role for CRTC2 in the transcriptional response to fasting, but indicate only a limited contribution of this cofactor to the maintenance of glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)55-62
Number of pages8
JournalCell Metabolism
Volume10
Issue number1
DOIs
StatePublished - Jul 8 2009
Externally publishedYes

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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