Glucose transporter 3 in neuronal glucose metabolism: Health and diseases

Neurons obtain glucose from extracellular environment for energy production mainly depending on glucose transporter 3 (GLUT3). GLUT3 uptakes glucose with high affinity and great transport capacity, and is important for neuronal energy metabolism. This review summarized the role of neuronal GLUT3 in brain metabolism, function and development under both physiological conditions and in diseases, aiming to provide insights into neuronal glucose metabolism and its effect on brain. GLUT3 stabilizes neuronal glucose uptake and utilization, influences brain development and function, and ameliorates aging-related manifestations. Neuronal GLUT3 is regulated by synaptic activity, hormones, nutrition, insulin and insulin-like growth factor 1 in physiological conditions, and is also upregulated by hypoxia-ischemia. GLUT3-related neuronal glucose and energy metabolism is possibly involved in the pathogenesis, pathophysiological mechanism, progression or prognosis of brain diseases, including Alzheimer's disease, Huntington's disease, attention-deficit/hyperactivity disorder and epilepsy. GLUT3 may be a promising therapeutic target of these diseases. This review also briefly discussed the role of other glucose transporters in neuronal glucose metabolism, which work together with GLUT3 to sustain and stabilize glucose and energy supply for neurons. Deficiency in these glucose transporters may also participate in brain diseases, especially GLUT1 and GLUT4.