Llagostera Martín, EstherCatalucci, DanieleMartí, LucLiesa Torre-Marín, MontserratCamps Camprubí, MartaCiaraldi, Theodore P.Kondo, RichardReddy, SitaDillmann, Wolfgang H.Palacín Prieto, ManuelZorzano Olarte, AntonioRuiz-Lozano, PilarGomis, Ramon, 1946-Kaliman, Perla2013-05-102013-05-102007-101932-6203https://hdl.handle.net/2445/43315Myotonic 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.11 p.application/pdfengcc-by (c) Llagostera Martín, Esther et al., 2007http://creativecommons.org/licenses/by/3.0/esFisiologia patològicaProteïnes quinasesMalalties de l'aparell locomotorInsulinaPathological physiologyProtein kinasesEnfermedades del aparato locomotorInsulininfo:eu-repo/semantics/article5678422013-05-10info:eu-repo/semantics/openAccess17987120