Intracerebroventricular administration of antisense oligodeoxynucleotide against GLUT2 glucose transporter mRNA reduces food intake, body weight change and glucoprivic feeding response in rats.
The GLUT2 glucose transporter, which may play a glucose-sensing role in hepatocyte and islet beta cells because of its low affinity and high Km for glucose, has been identified in some discrete brain areas that are related to feeding behavior and energy metabolism. We tested the hypothesis that brain GLUT2 may play a role in the control of food intake by antisense technology loss-of-function analysis. Antisense oligonucleotides directed against GLUT2 mRNA were administered intracerebroventricularly to eight rats daily for 13 days. Another eight rats were administered intracerebroventricularly with missense oligonucleotides as the control. Food intake was monitored by a computerized feeding system. Data were analyzed using a one-way general linear model or Mann-Whitney U test when appropriate. Cumulative food intake and body weight change in antisense-treated rats were significantly lower (18 and 160%, respectively) in the group treated with antisense oligonucleotides than in the group treated with missense control oligonucleotides. There was no increase in cumulative food intake in response to 2-deoxyglucose challenge in rats treated with antisense oligonucleotide, but in those treated with missense control oligonucleotide, cumulative food intake was fivefold greater in response to 2-deoxyglucose. These data suggest a possible role of brain GLUT2 in the regulation of food intake and body energy stores.
Wan
H Z
HZ
Department of Foods and Nutrition, The University of Georgia, Athens, GA 30602, USA.
Hulsey
M G
MG
Martin
R J
RJ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003847:Deoxyglucose / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism; D005247:Feeding Behavior / Q000187:drug effects; D005947:Glucose / Q000172:deficiency; D051273:Glucose Transporter Type 2; D007276:Injections, Intraventricular; D016014:Linear Models; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric
D051273:Glucose Transporter Type 2; D009004:Monosaccharide Transport Proteins; D016376:Oligonucleotides, Antisense; D003847:Deoxyglucose; D005947:Glucose