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Role of Myotonic Dystrophy Protein Kinase [DMPK] in Glucose Homeostasis and Muscle Insulin Action
Llagostera Martín, Esther; Catalucci, D.; Marti, L.; Liesa Torre-Marín, Montserrat; Camps Camprubí, Marta; Ciaraldi, T.; Kondo, R.; Reddy, S.; Dillmann, W.; Palacín Prieto, Manuel; Zorzano Olarte, Antonio; Rúiz Lozano, P.; Gomis, Ramon, 1946-; Kaliman, Perla
Universitat de Barcelona
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.
Fisiologia patològica
Proteïnes quinases
Malalties de l'aparell locomotor
Insulina
Pathological physiology
Protein kinases
Enfermedades del aparato locomotor
Insulin
cc-by (c) Llagostera Martín, Esther et al., 2007
http://creativecommons.org/licenses/by/3.0/es
Artículo
info:eu-repo/semantics/publishedVersion
Public Library of Science (PLoS)
         

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