| Autor: |
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 |
| Jazyk: |
angličtina |
| Rok vydání: |
2007 |
| Předmět: |
|
| Zdroj: |
PLoS ONE, Vol 2, Iss 11, p e1134 (2007) |
| Druh dokumentu: |
article |
| ISSN: |
1932-6203 |
| DOI: |
10.1371/journal.pone.0001134 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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