%0 Journal Article
%T Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action
%A Esther Llagostera
%A Daniele Catalucci
%A Luc Marti
%A Marc Liesa
%A Marta Camps
%A Theodore P. Ciaraldi
%A Richard Kondo
%A Sita Reddy
%A Wolfgang H. Dillmann
%A Manuel Palacin
%A Antonio Zorzano
%A Pilar Ruiz-Lozano
%A Ramon Gomis
%A Perla Kaliman
%J PLOS ONE
%D 2007
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0001134
%X Myotonic dystrophy 1 (DM1) is caused by a CTG expansion in the 3¡ä-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.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0001134