Role of myotonic dystrophy protein kinase (DMPK) in glucose homeostasis and muscle insulin action

Esther Llagostera, Daniele Catalucci, Luc Marti, Marc Liesa, Marta Camps, Theodore P. Ciaraldi, Richard Kondo, Sita Reddy, Wolfgang H. Dillmann, Manuel Palacin, Antonio Zorzano, Pilar Ruiz-Lozano, Ramon Gomis, Perla Kaliman

Research output: Contribution to journalArticle

Abstract

Myotonic dystrophy 1 (DM1) is caused by a CTG expansion in the 3′-unstranslated region of the DMPK gene, which encodes a serine/ threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk-/-) mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk-/- mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk-/- mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes.

Original languageEnglish
Article numbere1134
JournalPLoS One
Volume2
Issue number11
DOIs
Publication statusPublished - Nov 7 2007

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Llagostera, E., Catalucci, D., Marti, L., Liesa, M., Camps, M., Ciaraldi, T. P., Kondo, R., Reddy, S., Dillmann, W. H., Palacin, M., Zorzano, A., Ruiz-Lozano, P., Gomis, R., & Kaliman, P. (2007). Role of myotonic dystrophy protein kinase (DMPK) in glucose homeostasis and muscle insulin action. PLoS One, 2(11), [e1134]. https://doi.org/10.1371/journal.pone.0001134