Low density lipoprotein mimics insulin action on autophagy and glucose uptake in endothelial cells

Scientific Reports
Lin ZhuSi Jin

Abstract

Elevated plasma low density lipoprotein (LDL) is an established risk factor for cardiovascular disease. In addition to being able to cross the endothelial barrier to become accumulated in subendothelial space and thereby initiate atherosclerosis, LDL may exert a direct effect on vascular endothelial cells through activation of LDL receptor and its downstream signaling. Whether LDL can modulate the signaling for autophagy in endothelial cells is not clear. The present study firstly demonstrated that LDL can suppress endothelial autophagy through activation of the PI3K/Akt/mTOR signaling pathway and can promote glucose uptake by translocating glucose transporter 1 (GLUT1) from cytoplasm to cell membrane, actions similar to those of insulin. A co-immunoprecipitation assay found that LDL receptor (LDLR) and insulin receptor (IR) formed a complex in HUVECs. Knock down of the insulin receptor by small interfering RNA blocked the suppression of autophagy by LDL, as well as the signaling pathway involved. We conclude that LDL may mimic the action of insulin in endothelial cells, which might partly explain the increased incidence of diabetes in patients receiving some LDL-lowering therapy.

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Citations

Sep 24, 2020·The Journal of Physiological Sciences : JPS·Abdullah Al MamunMotohiko Sato
May 4, 2021·Frontiers in Cell and Developmental Biology·Jing XuDaisuke Koya
May 23, 2021·Molecular Biology Reports·Aybike Sena OzuynukNeslihan Coban

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Methods Mentioned

BETA
fluorescence microscopy
immunoprecipitation
co-immunoprecipitation

Software Mentioned

GraphPad Prism

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