Sodium valproate inhibits glucose transport and exacerbates Glut1-deficiency in vitro.
Anticonvulsant sodium valproate interferes with brain glucose metabolism. The mechanism underlying such metabolic disturbance is unclear. We tested the hypothesis that sodium valproate interferes with cellular glucose transport with a focus on Glut1 since glucose transport across the blood-brain barrier relies on this transporter. Cell types enriched with Glut1 expression including human erythrocytes, human skin fibroblasts, and rat astrocytes were used to study the effects of sodium valproate on glucose transport. Sodium valproate significantly inhibited Glut1 activity in normal and Glut1-deficient erythrocytes by 20%-30%, causing a corresponding reduction of Vmax of glucose transport. Similarly, in primary astrocytes as well as in normal and Glut1-deficient fibroblasts, sodium valproate inhibited glucose transport by 20%-40% (P < 0.05), accompanied by an up to 60% downregulation of GLUT1 mRNA expression (P < 0.05). In conclusion, sodium valproate inhibits glucose transport and exacerbates Glut1 deficiency in vitro. Our findings imply the importance of prudent use of sodium valproate for patients with compromised Glut1 function.
Wong
Hei Yi
HY
Department of Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
Chu
Tsui Shan
TS
Lai
Janice Ching
JC
Fung
Kwok Pui
KP
Fok
Tai Fai
TF
Fujii
Tatsuya
T
Ho
Yuan Yuan
YY
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors* / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014635:Valproic Acid / Q000494:pharmacology*
D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; C037626:3'-O-methylguanosine; D006151:Guanosine; D014635:Valproic Acid; D005947:Glucose