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Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action
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 expans...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2043489/ https://www.ncbi.nlm.nih.gov/pubmed/17987120 http://dx.doi.org/10.1371/journal.pone.0001134 |
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author | Llagostera, Esther Catalucci, Daniele Marti, Luc Liesa, Marc Camps, Marta Ciaraldi, Theodore P. Kondo, Richard Reddy, Sita Dillmann, Wolfgang H. Palacin, Manuel Zorzano, Antonio Ruiz-Lozano, Pilar Gomis, Ramon Kaliman, Perla |
author_facet | Llagostera, Esther Catalucci, Daniele Marti, Luc Liesa, Marc Camps, Marta Ciaraldi, Theodore P. Kondo, Richard Reddy, Sita Dillmann, Wolfgang H. Palacin, Manuel Zorzano, Antonio Ruiz-Lozano, Pilar Gomis, Ramon Kaliman, Perla |
author_sort | Llagostera, Esther |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2043489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-20434892007-11-07 Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action Llagostera, Esther Catalucci, Daniele Marti, Luc Liesa, Marc Camps, Marta Ciaraldi, Theodore P. Kondo, Richard Reddy, Sita Dillmann, Wolfgang H. Palacin, Manuel Zorzano, Antonio Ruiz-Lozano, Pilar Gomis, Ramon Kaliman, Perla PLoS One Research Article 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. Public Library of Science 2007-11-07 /pmc/articles/PMC2043489/ /pubmed/17987120 http://dx.doi.org/10.1371/journal.pone.0001134 Text en Llagostera et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Llagostera, Esther Catalucci, Daniele Marti, Luc Liesa, Marc Camps, Marta Ciaraldi, Theodore P. Kondo, Richard Reddy, Sita Dillmann, Wolfgang H. Palacin, Manuel Zorzano, Antonio Ruiz-Lozano, Pilar Gomis, Ramon Kaliman, Perla Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action |
title | Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action |
title_full | Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action |
title_fullStr | Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action |
title_full_unstemmed | Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action |
title_short | Role of Myotonic Dystrophy Protein Kinase (DMPK) in Glucose Homeostasis and Muscle Insulin Action |
title_sort | role of myotonic dystrophy protein kinase (dmpk) in glucose homeostasis and muscle insulin action |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2043489/ https://www.ncbi.nlm.nih.gov/pubmed/17987120 http://dx.doi.org/10.1371/journal.pone.0001134 |
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