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Title: Role of Myotonic Dystrophy Protein Kinase [DMPK] in Glucose Homeostasis and Muscle Insulin Action
Author: 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
Keywords: Fisiologia patològica
Proteïnes quinases
Malalties de l'aparell locomotor
Pathological physiology
Protein kinases
Enfermedades del aparato locomotor
Issue Date: Oct-2007
Publisher: Public Library of Science (PLoS)
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: PLoS One, 2007, num. 11, p. e1134
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
Articles publicats en revistes (Medicina)

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