Effects of ethanol ingestion on glucose transporter-1 protein and mRNA levels in rat brain.
In the normal adult brain, glucose provides 90% of the energy requirement, as well as substrate for nucleic acid and lipid synthesis. We have previously observed that ethanol impairs hexose uptake by rat astrocytes in culture. In the present study, male Sprague-Dawley rats, 200-250 g, were fed liquid diet in which 36% of the calories were derived from ethanol (EF) for 4 weeks. Controls were fed ad libitum (AF) or pair-fed (PF) an equicaloric diet without ethanol. Blood glucose levels did not differ between the groups at the time of study. Glucose transport by brain plasma membranes was characterized by cytochalasin B binding and showed a slight increase in transporter number (mean +/- SEM of 4 experiments = 76.4 +/- 2.5 pmoles/mg protein in EF vs. 69.5 +/- 1.0 in PF) with no change in affinity (1.8 +/- 0.1 nM-1 in EF and 1.6 +/- 0.1 in PF). Glucose transporter, GLUT-1, was increased on Western blots. In contrast, Northern analysis of cortical tissue, using a rat brain glucose transporter cDNA insert (1.59 kb Bgl II fragment of pSPGT-1), showed a 23 to 35% decrease in steady-state levels of glucose transporter mRNA. GLUT-1 mRNA, localized in brain sections by in situ hybridization histochemistry, showed marked reductions in choroid plexus and hippocampus following ethanol treatment. Ethanol appears to have multiple effects on brain GLUT-1.
Singh
S P
SP
Endocrine-Metabolic Division, Veterans Affairs Medical Center, North Chicago, Illinois 60064.
Srivenugopal
K S
KS
Yuan
X H
XH
Jiang
F
F
Snyder
A K
AK
D000437:Alcoholism / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D051272:Glucose Transporter Type 1; D017403:In Situ Hybridization; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat