Open AccessNeutral ceramidase‐enriched exosomes prevent palmitic acid‐induced insulin resistance in H4 IIEC 3 hepatocytes
Author(s) -
Zhu Qun,
Zhu Rongping,
Jin Junfei
Publication year - 2016
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12125
Subject(s) - insulin resistance , ceramide , palmitic acid , insulin , microvesicles , chemistry , irs1 , reactive oxygen species , medicine , insulin receptor , biochemistry , endocrinology , biology , apoptosis , fatty acid , microrna , gene
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 H4 IIEC 3 hepatocytes. Recently, we found that exosomes secreted from INS ‐1 cells that were transfected with neutral ceramidase ( NCD ase) plasmids had raised NCD ase activity; these NCD ase‐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 H4 IIEC 3 cells. Moreover, NCD ase‐enriched exosomes from INS ‐1 cells rescued PA ‐induced H4 IIEC 3 insulin resistance and blocked PA ‐induced reactive oxygen species production in which ceramide was involved.