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Cdc2-like kinase 2 is an insulin-regulated suppressor of hepatic gluconeogenesis

Joseph T Rodgers1, Wilhelm Haas, Steven P Gygi

  • 1Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

Cell Metabolism
|January 16, 2010
PubMed

Insights

Cdc2-like kinase 2 (Clk2) suppresses liver glucose production by regulating PGC-1alpha. This finding reveals Clk2

Area of Science:

  • Molecular Biology
  • Metabolic Regulation
  • Signal Transduction

Background:

  • Insulin signaling and metabolic gene expression are crucial for nutrient homeostasis.
  • Dysregulation of these pathways contributes to insulin resistance and metabolic diseases.
  • The link between insulin signal transduction and metabolic response requires further elucidation.

Purpose of the Study:

  • To investigate the role of Cdc2-like kinase 2 (Clk2) in hepatic glucose metabolism.
  • To identify Clk2 as a novel component linking insulin signaling to metabolic regulation.

Main Methods:

  • Investigated Clk2 protein levels and kinase activity.
  • Examined the effect of insulin/Akt pathway on Clk2 during hepatic refeeding.
  • Assessed Clk2's direct phosphorylation of PGC-1alpha and its impact on gene expression.
  • Studied Clk2's role in db/db mouse model of diabetes.

Main Results:

  • Clk2 protein levels and kinase activity are induced by insulin/Akt pathway during hepatic refeeding.
  • Clk2 directly phosphorylates PGC-1alpha, repressing gluconeogenic gene expression and hepatic glucose output.
  • Clk2 is downregulated in db/db mice, and its reintroduction improves glycemic control.

Conclusions:

  • Clk2 acts as an insulin-regulated suppressor of hepatic gluconeogenesis and glucose output.
  • Clk2 is a key regulator linking hepatic insulin signaling to glucose metabolism.
  • Targeting Clk2 may offer therapeutic potential for managing hyperglycemia in insulin resistance.

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