INTRACEREBROVENTRICULAR ADMINISTRATION OF ANTISENSE OLIGODEOXYNUCLEOTIDE AGAINST GLUT2 GLUCOSE-TRANSPORTER MESSENGER-RNA REDUCES FOOD-INTAKE, BODY-WEIGHT CHANGE AND GLUCOPRIVIC FEEDING RESPONSE IN RATS

The GLUT2 glucose transporter, which may play a glucose-sensing role i n hepatocyte and islet beta cells because of its low affinity and high K-m for glucose, has been identified in some discrete brain areas tha t are related to feeding behavior and energy metabolism. We tested the hypothesis that brain GLUT2 may play a role in the control of food in take by antisense technology loss-of-function analysis. Antisense olig onucleotides directed against GLUT2 mRNA were administered intracerebr oventricularly to eight rats daily for 13 days, Another eight rats wer e administered intracerebroventricularly with missense oligonucleotide s as the control, Food intake was monitored by a computerized feeding system, Data were analyzed using a one-way general linear model or Man n-Whitney U test when appropriate, Cumulative food intake and body wei ght change in antisense-treated rats were significantly lower (18 and 160%, respectively) in the group treated with antisense oligonucleotid es than in the group treated with missense control oligonucleotides, T here was no increase in cumulative food intake in response to 2-deoxyg lucose challenge in rats treated with antisense oligonucleotide, but i n 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 inta ke and body energy stores.