ANG II increases 2-deoxyglucose uptake in mouse embryonic stem cells

Abstract

It is now suggested that all components of the renin–angiotensin system are present in many tissues, including the embryo and may play a major role in embryo development and differentiation. However, little is known regarding whether ANG II regulates glucose transport in mouse embryonic stem (ES) cells. Thus, the effects of ANG II on [ 3H]-2-deoxyglucose (2-DG) uptake and its related signal pathways were examined in mouse ES cells. ANG II significantly increased cell proliferation and 2-DG uptake in concentration- and time-dependent manner (> 18 h, > 10 − 8 M) and increased mRNA and protein level of GLUT1 by 31 ± 7% and 22 ± 5% compared to control, respectively. Actinomycin D and cycloheximide completely blocked the effect of ANG II on 2-DG uptake. ANG II-induced increase of 2-DG uptake was blocked by losartan, an ANG II type 1 (AT 1) receptor blocker, but not by PD 123319, an ANG II type 2 (AT 2) receptor blocker. In addition, ANG II-induced stimulation of 2-DG uptake was attenuated by phospholipase C (PLC) inhibitors, neomycin and U 73122 and ANG II increased inositol phosphates (IPs) formation by 37 ± 8% of control. Protein kinase C (PKC) inhibitors, staurosporine, bisindolylmaleimide I, and H-7 also blocked ANG II-induced stimulation of 2-DG uptake. Indeed, ANG II activated a PKC translocation from the cytosolic to membrane fraction, suggesting a role of PKC. A 23187 (Ca 2+ ionophore) increased 2-DG uptake and nifedifine (L-type Ca 2+ channel blocker) blocked it. In conclusion, ANG II increased 2-DG uptake by PKC activation via AT 1 receptor in mouse ES cells.