After its uptake into the cytosol, intracellular glucose is phosphorylated to glucose-6-phosphate (G6P), trapping it within the cell and preparing it for metabolism. In glucose-exporting tissues, like liver, G6P is transported into the ER, where it is dephosphorylated by G6Pase-α. The glucose is then returned to the cytosol for export [1, 2]. Defects in these pathways cause glycogen storage diseases [1]. G6Pase-β, an isozyme of G6Pase-α, is widely expressed [3, 4]. Its role in cells that do not export glucose is unclear, although mutations in G6Pase-β cause severe and widespread abnormalities [5-7]. Astrocytes, the most abundant cells in the brain, provide metabolic support to neurons, facilitated by astrocytic endfeet that contact blood capillaries or neurons [8-12]. Perivascular endfeet are the main site of glucose uptake by astrocytes [13], but in human brain they may be several millimeters away from the perineuronal processes [14]. We show that cultured human fetal astrocytes express G6Pase-β, but not G6Pase-α. ER-targeted glucose sensors [15, 16] reveal that G6Pase-β allows the ER of human astrocytes to accumulate glucose by importing G6P from the cytosol. Glucose uptake by astrocytes, ATP production, and Ca2+ accumulation by the ER are attenuated after knockdown of G6Pase-β using lentivirus-delivered shRNA and substantially rescued by expression of G6Pase-α. We suggest that G6Pase-β activity allows effective uptake of glucose by astrocytes, and we speculate that it allows the ER to function as an intracellular "highway" delivering glucose from perivascular endfeet to the perisynaptic processes.
Pubmed ID: 30415704 RIS Download
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View all literature mentionsA commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
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View all literature mentionsCell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis polyclonal targets glucose-6-phosphatase, catalytic subunit
View all literature mentionsThis polyclonal targets Mouse GFAP
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis polyclonal targets donkey anti-mouse IgG-HRP
View all literature mentionsThis polyclonal targets Slc37a4
View all literature mentionsThis monoclonal targets G6Pase-beta (H-143)
View all literature mentionsThis polyclonal targets Mouse GFAP
View all literature mentionsThis unknown targets Goat IgG (H+L)
View all literature mentionsThis polyclonal targets glucose-6-phosphatase, catalytic subunit
View all literature mentionsThis monoclonal targets G6Pase-beta (H-143)
View all literature mentionsThis polyclonal targets Rabbit IgG
View all literature mentionsThis polyclonal targets donkey anti-mouse IgG-HRP
View all literature mentionsThis polyclonal targets Slc37a4
View all literature mentions