2026-04-19T16:13:13Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1258902025-11-19T20:41:43Zcom_2072_1057col_2072_478781col_2072_478799col_2072_478916col_2072_478908col_2072_478917

00925njm 22002777a 4500 dc Hernández-Alvarez, María Isabel author Díaz Ramos, M. Àngels author Berdasco, María author Cobb, Jeff author Planet, Evarist author Cooper, Diane author Pazderska, Agnieszka author Wanic, Krzystof author O'Hanlon, Declan author Gómez, Antonio author Ballina, Laura R. de la author Esteller, Manel author Palacín Prieto, Manuel author O'Gorman, Donal J. author Nolan, John J. author Zorzano Olarte, Antonio author 2018-11-07T15:17:23Z 2018-11-07T15:17:23Z 2017-10-23 2018-11-07T15:17:23Z 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. Diabetis Expressió gènica Seqüència d'aminoàcids Diabetes Gene expression Amino acid sequence Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism