Please use this identifier to cite or link to this item:
http://hdl.handle.net/2445/125890
Title: | Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism |
Author: | Hernández-Alvarez, María Isabel Díaz Ramos, M. Àngels Berdasco, María Cobb, Jeff Planet, Evarist Cooper, Diane Pazderska, Agnieszka Wanic, Krzystof O'Hanlon, Declan Gómez, Antonio Ballina, Laura R. de la Esteller, Manel Palacín Prieto, Manuel O'Gorman, Donal J. Nolan, John J. Zorzano Olarte, Antonio |
Keywords: | Diabetis Expressió gènica Seqüència d'aminoàcids Diabetes Gene expression Amino acid sequence |
Issue Date: | 23-Oct-2017 |
Publisher: | Nature Publishing Group |
Abstract: | The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis revealed increased levels of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from the disruption of muscle BCAA management. Our data support the view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of the pathophysiology of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes. |
Note: | Reproducció del document publicat a: https://doi.org/10.1038/s41598-017-14120-6 |
It is part of: | Scientific Reports, 2017, vol. 7, p. 13850 |
URI: | http://hdl.handle.net/2445/125890 |
Related resource: | https://doi.org/10.1038/s41598-017-14120-6 |
ISSN: | 2045-2322 |
Appears in Collections: | Articles publicats en revistes (Ciències Fisiològiques) Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) Publicacions de projectes de recerca finançats per la UE |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
676875.pdf | 2.08 MB | Adobe PDF | View/Open |
This item is licensed under a
Creative Commons License