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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/43315
Role of Myotonic Dystrophy Protein Kinase [DMPK] in Glucose Homeostasis and Muscle Insulin Action
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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.
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LLAGOSTERA MARTÍN, Esther, CATALUCCI, Daniele, MARTÍ, Luc, LIESA TORRE-MARÍN, Montserrat, CAMPS CAMPRUBÍ, Marta, CIARALDI, Theodore p., KONDO, Richard, REDDY, Sita, DILLMANN, Wolfgang h., PALACÍN PRIETO, Manuel, ZORZANO OLARTE, Antonio, RUIZ-LOZANO, Pilar, GOMIS, Ramon, KALIMAN, Perla. Role of Myotonic Dystrophy Protein Kinase [DMPK] in Glucose Homeostasis and Muscle Insulin Action. _PLoS One_. 2007. Vol. 11, núm. e1134. [consulta: 23 de gener de 2026]. ISSN: 1932-6203. [Disponible a: https://hdl.handle.net/2445/43315]