期刊
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
卷 307, 期 9, 页码 C774-C787出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpcell.00110.2014
关键词
myotubes; 2-D DIGE; proteasome; protein synthesis; glucose incorporation into glycogen; palmitate oxidation; carbonylation; ubiquitin; bortezomib; Velcade
资金
- Center for Gender Medicine at Karolinska Institutet
- Swedish Research Council
- Swedish Society of Medicine
- Ake Wiberg Foundation
- Magnus Bergvalls Foundation
- Fredrik and Ingrid Thurings Foundation
- Knut and Alice Wallenberg Foundation [2005.0120]
- Strategic Research Programme in Diabetes at Karolinska Institutet
- European Research Council Ideas Program (ICEBERG) [ERC-2008-AdG23285]
Two-dimensional difference gel electrophoresis (2-D DIGE)-based proteome analysis has revealed intrinsic insulin resistance in myotubes derived from type 2 diabetic patients. Using 2-D DIGE-based proteome analysis, we identified a subset of insulin-resistant proteins involved in protein turnover in skeletal muscle of type 2 diabetic patients, suggesting aberrant regulation of the protein homeostasis maintenance system underlying metabolic disease. We then validated the role of the ubiquitin-proteasome system (UPS) in myotubes to investigate whether impaired proteasome function may lead to metabolic arrest or insulin resistance. Myotubes derived from muscle biopsies obtained from people with normal glucose tolerance (NGT) or type 2 diabetes were exposed to the proteasome inhibitor bortezomib (BZ; Velcade) without or with insulin. BZ exposure increased protein carbonylation and lactate production yet impaired protein synthesis and UPS function in myotubes from type 2 diabetic patients, marking the existence of an insulin-resistant signature that was retained in cultured myotubes. In conclusion, BZ treatment further exacerbates insulin resistance and unmasks intrinsic features of metabolic disease in myotubes derived from type 2 diabetic patients. Our results highlight the existence of a confounding inherent abnormality in cellular protein dynamics in metabolic disease, which is uncovered through concurrent inhibition of the proteasome system.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据