Ultrastructural localization of GLUT 1 and GLUT 3 glucose transporters in rat brain

Abstract

Precise localization of glucose transport proteins in the brain has proved difficult, especially at the ultrastructural level. This has limited further insights into their cellular specificity, subcellular distribution, and function. In the present study, preembedding ultrastructural immunocytochemistry was used to localize the major brain glucose transporters, GLUTs 1 and 3, in vibratome sections of rat brain. Our results support the view that, besides being present in endothelial cells of central nervous system (CNS) blood vessels, GLUT 1 is present in astrocytes. GLUT 1 was detected in astrocytic end feet around blood vessels, and in astrocytic cell bodies and processes in both gray and white matter. GLUT 3, the neuronal glucose transporter, was located primarily in pre- and postsynaptic nerve endings and in small neuronal processes. This study: (1) affirms that GLUT 3 is neuron-specific, (2) shows that GLUT 1 is not normally expressed in detectable quantities by neurons, (3) suggests that glucose is readily available for synaptic energy metabolism based on the high concentration of GLUT 3 in membranes of synaptic terminals, and (4) demonstrates significant intracellular and mitochondrial localization of glucose transport proteins.

Characterisation of glucose transporters in the intact coronary artery endothelium in rats: GLUT-2 upregulated by long-term hyperglycaemia

“…3i) and GLUT-4 labelling in adipocytes (Fig. 3j), as shown by other authors [25]. Lastly, we looked at the distribution of GLUT-2, GLUT-5 and SGLT-1 in epithelial cells of the jejunum, a tissue for which the glucose transporter organisation is well established [18].…”

The facilitative glucose transporter GLUT3: 20 years of distinction

“…However, as is evident in Fig. 1, which depicts rat cerebellar granule neurons in culture and pyramidal neurons in human hippocampus, labeling is evident in axons and dendrites as well as in the neuronal cell bodies (44,71,75,78,82,84,128).…”

“…Numerous studies, predominantly in rodent brain, concluded that glucose delivery and utilization in the mammalian brain is mediated primarily by both GLUT1 and GLUT3: a high molecular weight form of GLUT1 in the endothelial cells of the microvessels that comprise the blood-brain barrier (BBB), GLUT3 in all neuronal populations, and a lower-molecularweight, less glycosylated form of GLUT1 in the remainder of the brain parenchyma (71,85,108,128).…”

Brain Lactate Metabolism: The Discoveries and the Controversies

“…Upregulation of the GLUT3 protein level is slower than cell-surface translocation, and is stimulated in vivo by conditions that affect CMR glc in the brain (Table 5). Glucose transport into neurons is critical for brain function, and in the adult rat brain, GLUT3 is localized in synaptic terminals, small neuronal processes, and postsynaptic structures, with significant intracellular localization (Leino et al, 1997). Glucose transporter-3 deficiency causes serious developmental abnormalities in mice (Table 5).…”

“…Postsynaptic densities contain glycolytic enzymes that synthesize ATP (Wu et al, 1997), and GLUT3 is localized in synaptic endings and postsynaptic structures (Leino et al, 1997). Calcium clearance in activated cultured cerebellar granule neurons and in Purkinje cells in brain slices relies on glycolysis to power the plasma membrane Ca 2 + -ATPase in the soma, dendrites, and spines, and inhibition of mitochondrial ATP generation does not affect operation of this pump (Ivannikov et al, 2010).…”