Endothelin-1 regulates glucose utilization in cultured astrocytes by controlling intercellular communication through gap junctions
✍ Scribed by Arantxa Tabernero; Christian Giaume; José M. Medina
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 1017 KB
- Volume
- 16
- Category
- Article
- ISSN
- 0894-1491
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✦ Synopsis
The role played by endothelin-1 and intercellular communication mediated by gap junctions in the regulation of glucose disposal by astrocytes has been studied in primary culture. Endothelin-1 increased glucose uptake by astrocytes as did one of its putative messenger arachidonic acid and the non-physiological gap junction uncoupler a-glycyrrhetinic acid (AGA). None of these agents increased glucose uptake by C6 glioma cells, a cell line in which gap junction proteins are poorly expressed. In confluent astrocytes, the inhibition of gap junction permeability caused by AGA doubled the activity of the pentose phosphate shunt with minimal changes in the activity of the pyruvate dehydrogenase-catalyzed reaction and that of the tncarboxylic acid cycle. By contrast, these effects were not observed in dissociated astrocytes in which intercellular communication is lacking. The scraped loading dye transfer technique was modified to follow the passage of glucose and its metabolites through astrocyte gap junctions. The diffusion of glucose, the phosphorylated derivative glucose-6-phosphate, the phosphorylisable but not metabolisable derivative ortho-methyl-glucose, and the anaerobic glycolytic product L-lactate was much higher in astrocytes than in C6 glioma cells and was inhibited by the inhibition of gap junction permeability caused by endothelin-1, arachidonic acid, octanol, or AGA. It is concluded that gap junction permeability may regulate brain metabolism by conti-olling the uptake, utilization, and intercellular distribution of glucose and its metabolites in astrocytes.