Brain glucose transporters Implications for neurologic disease

The normal adult brain constitutes approximately 2% of the body weight and consumes approximately 20% of glucose in the body (about 120 g of glucose per day). In the nervous system, the aerobic metabolism of glucose is the main source of energy in the form of adenosine triphosphate (ATP); most of this energy is utilized to sustain excitatory synaptic transmission. The interaction among neurons, astrocytes, and endothelial cells has a central role coupling energy supply with changes in neuronal activity. These cells express different subtypes of glucose transporters (GLUTs) that mediate the sodium-independent facilitated transport of glucose across membranes. GLUT1 and GLUT3 are expressed in the nervous system, GLUT1 in endothelial cells and astrocytes, and GLUT3 in neurons. Astrocytes take up glucose from the blood and metabolize it to lactate, which is then delivered to neurons. The relative contribution of this astrocyte-to-neuron lactate shuttle as a main source of energy to sustain neuronal physiology, compared to direct glucose uptake by neurons, is a matter of debate; nevertheless, the role of GLUT1 in astrocytes is underscored by the range of clinical phenotypes associated with GLUT1 deficiency. There are several reviews on the biochemistry and physiology of GLUTs, neurometabolic coupling between astrocytes and neurons, the clinical consequences of GLUT1 deficiency, and the involvement of GLUT1 in other neurologic disorders.(1-7</SUP)