ATP2B1 gene Silencing Increases Insulin Sensitivity through Facilitating Akt Activation via the Ca2+ /calmodulin Signaling Pathway and Ca2+ -associated eNOS Activation in Endothelial Cells

International Journal of Biological Sciences
Yang LongYong Xu

Abstract

Endothelial cell insulin resistance may be partially responsible for the higher risk of atherosclerosis and cardiovascular disease in populations with insulin resistance and type 2 diabetes mellitus (T2DM). A genome-wide association study revealed a significant association between the ATPase plasma membrane Ca2+ transporting 1 (ATP2B1) gene and T2DM in two community-based cohorts from the Korea Association Resource Project. However, little is known about the implication of the ATP2B1 gene on T2DM. In the present study, we investigated the role of the ATP2B1 gene in endothelial cell insulin sensitivity. ATP2B1 gene silencing resulted in enhanced intracellular calcium concentrations and increased insulin-induced Akt activation compared to that in the negative siRNA-transfected HUVECs (Human Umbilical Vein Endothelial Cells). The elevated insulin sensitivity mediated by ATP2B1 gene silencing was Ca2+/calmodulin-dependent, as verified by administration of the calcium chelator BAPTA-AM or the calmodulin-specific antagonist W7. Moreover, higher levels of phosphorylation of eNOS (Ser1177) were observed in ATP2B1-silenced HUVECs. In addition to BAPTA-AM and W7, L-NAME, an eNOS antagonist, abolished insulin-induced Akt phosphorylation a...Continue Reading

Citations

Jun 13, 2020·Journal of the Science of Food and Agriculture·Te-Hua LiuTsung-Yu Tsai
Dec 28, 2019·International Journal of Molecular Sciences·Chi-Ming ChanChi-Feng Hung
Mar 31, 2021·Journal of Molecular and Cellular Cardiology·Alexandra NjegicElizabeth J Cartwright
Nov 14, 2020·Journal of Biomolecular Structure & Dynamics·Rohit Karn, Isaac Arnold Emerson

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Methods Mentioned

BETA
transfection
Protein Assay
co-immunoprecipitation
fluorescence assay
nuclear magnetic resonance
pulldown
gene knockdown
gene knockout

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