Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism.
Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism.
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DOI：
10.1038/s41598-017-14120-6
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发表时间：
2017-10-23
影响因子：
4.6
通讯作者：
Zorzano A
中科院分区：
文献类型：
--
作者：
Hernández-Alvarez MI;Díaz-Ramos A;Berdasco M;Cobb J;Planet E;Cooper D;Pazderska A;Wanic K;O'Hanlon D;Gomez A;de la Ballina LR;Esteller M;Palacin M;O'Gorman DJ;Nolan JJ;Zorzano A
2 型糖尿病病理生理学特征的分子机制尚不完全清楚。在这里，我们对经典型和早发型 2 型糖尿病 (T2D) 受试者的骨骼肌和血浆代谢组学进行了转录组分析。还在 ob/ob 和 db/db 小鼠的组织中进行了重点研究。我们记录了 T2D，无论是早发型还是晚发型，其特征都是参与支链氨基酸 (BCAA) 代谢的基因的肌肉表达减少。加权共表达网络分析支持以下观点：BCAA 基因与 2 型糖尿病的病理生理学相关，并且 T2D 患者骨骼肌中线粒体 BCAA 管理受损。在糖尿病小鼠模型中，我们检测到参与支链氨基酸代谢的骨骼肌蛋白发生变化，但在肥胖小鼠中没有检测到。代谢组学分析显示，T2D 患者血浆中支链酮酸 (BCKA) 和 BCAA 水平升高，这可能是由于肌肉 BCAA 管理中断所致。我们的数据支持这样的观点，即骨骼肌中参与 BCAA 处理的基因的抑制是 2 型糖尿病病理生理学的一部分，这种情况在早发性糖尿病和经典 2 型糖尿病中都会发生。
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.
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WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
--
作者：
Abdul-Ghani MA;DeFronzo RA
通讯作者：
DeFronzo RA
影响因子：
8.1
作者：
Lerin C;Goldfine AB;Boes T;Liu M;Kasif S;Dreyfuss JM;De Sousa-Coelho AL;Daher G;Manoli I;Sysol JR;Isganaitis E;Jessen N;Goodyear LJ;Beebe K;Gall W;Venditti CP;Patti ME
通讯作者：
Patti ME
影响因子：
29
作者：
Newgard CB
通讯作者：
Newgard CB
影响因子：
8.2
作者：
Giesbertz, Pieter;Padberg, Inken;Daniel, Hannelore
通讯作者：
Daniel, Hannelore