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GRK2 is a tonic inhibitor of Akt/eNOS signaling in human vascular endothelial cells under conditions of hyperglycemia with high insulin levels (851.12)
Author(s) -
Sakata Kimimasa
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.851.12
Subject(s) - enos , protein kinase b , beta adrenergic receptor kinase , medicine , endocrinology , insulin , chemistry , endothelial dysfunction , umbilical vein , insulin receptor , receptor , signal transduction , microbiology and biotechnology , nitric oxide , biology , insulin resistance , nitric oxide synthase , biochemistry , g protein coupled receptor , in vitro
The pathological role of GRK2 in vascular endothelial cell dysfunction was examined using human umbilical venous endothelial cells (HUVECs) exposed to high glucose and high insulin (HG/HI) in order to mimic insulin‐resistant diabetic conditions. GRK2 expression, membrane translocation, and activity were up‐regulated under HG/HI conditions. HG/HI did not activate Akt and eNOS, but GRK2 inhibitor or siRNA resulted in a significant increase in Akt and eNOS activation in HUVECs exposed to HG/HI. ERK1/2 activation was significantly increased after exposure to HG/HI, and the increase was prevented by GRK2 inhibitor or siRNA. In HEK293T cells which overexpressed GRK2, Akt activity was unchanged, while ERK1/2 activity was significantly raised. These data suggest that GRK2, which is up‐regulated under HG/HI conditions, leads to a tonic inhibition of the insulin downstream effectors, Akt and eNOS, with an increasing effect on ERK1/2 activity in endothelial cells.