Endothelin-1 stimulates the translocation and upregulation of both glucose transporter and hexokinase in astrocytes: relationship with gap junctional communication.
We have previously shown that endothelin-1 increases glucose uptake in astrocytes. In the present work we investigate the mechanism through which endothelin-1 (ET-1) increases glucose uptake. Our results show that ET-1 activates a short-term and a long-term mechanism. Thus, ET-1 induced a rapid change in the localization of both GLUT-1 and type I hexokinase. These changes are probably aimed at rapidly increasing the entry and phosphorylation of glucose. In addition, ET-1 upregulated GLUT-1 and type I hexokinase and induced the expression of isoforms not normally expressed in astrocytes, such as GLUT-3 and type II hexokinase. These changes provide astrocytes with the machinery required to sustain a high rate of glucose uptake for a longer period of time. Our previous work had suggested that the effect of ET-1 on glucose uptake was associated with the inhibition of gap junctions. In this work, we compare the effect of ET-1 with that of carbenoxolone, a classical inhibitor of gap junction communication. Carbenoxolone increased glucose uptake to the same extent as ET-1 following the same mechanisms. Thus, carbenoxolone induced a rapid change in the localization of both GLUT-1 and type I hexokinase, upregulated GLUT-1 and type I hexokinase and induced the expression of GLUT-3 and type II hexokinase. When the inhibition of gap junction was prevented by tolbutamide, neither ET-1 nor carbenoxolone were able to increase the levels of GLUT-1, GLUT-3, type I hexokinase or type II hexokinase, indicating that these events are closely related to gap junctions.
Sánchez-Alvarez
Rosa
R
Departamento de Bioquímica y Biología Molecular, Universidad de Salamanca, Spain.
Tabernero
Arantxa
A
Medina
José M
JM
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000493:pharmacokinetics; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006593:Hexokinase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008870:Microtubules / Q000201:enzymology; D008928:Mitochondria / Q000201:enzymology; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014044:Tolbutamide / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D019332:Endothelin-1; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D014044:Tolbutamide; D006593:Hexokinase; D005947:Glucose; D002229:Carbenoxolone