期刊
FEBS OPEN BIO
卷 6, 期 11, 页码 1078-1084出版社
WILEY-BLACKWELL
DOI: 10.1002/2211-5463.12125
关键词
ceramide; exosome; insulin resistance; neutral ceramidase; palmitic acid; reactive oxygen species
资金
- National Natural Science Foundation of China [81360309, 81572738, 81270898]
- Natural Science Foundation of Guangxi [2014GXNSFAA118194, 2015GXNSFEA139003]
- Jiangsu Provincial Natural Science Foundation [BK20151577]
- Medical Health Appropriate Technology Research and Development Project from the Health and Family Planning Commission in Guangxi [S201407-06]
- Scientific Research and Technology Development Project of Guilin [20140310-2-1]
- 'Sphingolipids and Related Diseases' Program for Innovative Research Team of Guilin Medical University
- Hundred Talents Program 'the Introduction of Overseas High-Level Talents in Colleges and Universities in Guangxi'
Oversupply of free fatty acids such as palmitic acid (PA) from the portal vein may cause liver insulin resistance. Production of reactive oxygen species plays a pivotal role in PA-induced insulin resistance in H4IIEC3 hepatocytes. Recently, we found that exosomes secreted from INS-1 cells that were transfected with neutral ceramidase (NCDase) plasmids had raised NCDase activity; these NCDase-enriched exosomes could inhibit PA-induced INS-1 cell apoptosis. Here, we showed that PA reduced insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 2 and decreased insulin-stimulated uptake of the fluorescent glucose analog 2-NBDG, confirming that insulin resistance occurred in PA-treated H4IIEC3 cells. Moreover, NCDase-enriched exosomes from INS-1 cells rescued PA-induced H4IIEC3 insulin resistance and blocked PA-induced reactive oxygen species production in which ceramide was involved.
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