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Updated: Jun 4, 2026
10:35
Extracellular Glucose Depletion as an Indirect Measure of Glucose Uptake in Cells and Tissues Ex Vivo
Published on: April 6, 2022
Activity-dependent regulation of surface glucose transporter-3
Jainne M Ferreira1, Arthur L Burnett, Gerald A Rameau
1Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA.
Summary
Neuronal activity increases glucose transporter 3 (GLUT3) on neuron surfaces, boosting glucose uptake. This process involves NMDA receptors and nitric oxide synthase, regulating energy supply for brain function.
Area of Science:
- Neuroscience
- Cell Biology
- Metabolism
Background:
- Glucose transporter 3 (GLUT3) is crucial for neuronal energy supply.
- The regulation of glucose influx by neuronal activity remains unclear.
Purpose of the Study:
- To investigate how synaptic stimulation influences GLUT3 surface expression and glucose uptake in neurons.
- To elucidate the molecular mechanisms controlling activity-dependent glucose transport.
Main Methods:
- Primary cultured cortical and hippocampal neurons were used.
- Experiments involved synaptic stimulation, NMDA receptor (NMDAR) and neuronal nitric oxide synthase (nNOS) inhibition, Akt inhibitor treatment, and analysis of GLUT3 surface expression.
- cGMP-dependent protein kinase (cGK) activation and inhibition were also studied.
Main Results:
- Synaptic activity elevated GLUT3 surface expression and intracellular glucose levels.
- NMDAR and nNOS inhibition blocked this effect.
- Akt inhibition prevented NMDAR-induced GLUT3 expression, while nNOS phosphorylation enhanced it.
- cGK activation increased GLUT3 surface expression, which was inhibited by Rp-8-pCPT-cGMPS.
Conclusions:
- NMDAR/Akt-dependent nNOS phosphorylation regulates GLUT3 trafficking.
- Activity-dependent GLUT3 trafficking is mediated by the NMDAR pathway.
- This mechanism provides a novel way to control neuronal energy supply and maintain glucose homeostasis during synaptic transmission.
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