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

Area of Science:

• Developmental Biology
• Cellular Physiology
• Endocrinology

Background:

• The renin-angiotensin system is present in embryonic tissues and may influence development.
• The role of Angiotensin II (ANG II) in regulating glucose transport in mouse embryonic stem (ES) cells is largely unknown.
• Understanding nutrient regulation is critical for early embryonic development.

Purpose of the Study:

• To investigate the effects of ANG II on glucose uptake in mouse ES cells.
• To elucidate the signaling pathways involved in ANG II-mediated glucose transport regulation.

Main Methods:

• Measured [3H]-2-deoxyglucose (2-DG) uptake and cell proliferation in mouse ES cells.
• Assessed mRNA and protein levels of GLUT1.
• Utilized receptor blockers (losartan, PD 123319), enzyme inhibitors (Actinomycin D, cycloheximide, PLC inhibitors, PKC inhibitors), and a Ca2+ ionophore/channel blocker.

Main Results:

• ANG II significantly increased 2-DG uptake and cell proliferation in a dose- and time-dependent manner.
• ANG II elevated GLUT1 mRNA and protein levels.
• The effects were mediated via the Angiotensin II type 1 (AT1) receptor, involving phospholipase C (PLC), protein kinase C (PKC) activation, and calcium signaling.

Conclusions:

• ANG II enhances glucose uptake and proliferation in mouse ES cells.
• This process is primarily mediated by the AT1 receptor, leading to PKC activation and subsequent modulation of glucose transporter expression and function.
• These findings highlight a novel role for the renin-angiotensin system in regulating nutrient metabolism during early embryonic development.