Several genes involved in glucosensing of the endocrine pancreas have been proposed to serve a similar function in the brain. These genes include the glucose transporter-2 (Glut-2) and glucokinase (GK). In addition, the glucagon-like peptide 1 receptor, which serves as a downstream signal modulator in pancreatic glucosensing and centrally alters feeding, is also of interest. We used quantitative real-time RT-PCR to measure changes in hypothalamic and brainstem Glut-2, GK, and Glp-1R expression of these genes induced by food restriction and refeeding. Sprague-Dawley rats were 50% food restricted for 1 day; one-half of the food-restricted rats were refed with chow for 1 hr before sacrifice. In both hypothalamus and brainstem, gene expression of Glut-2, GK, and Glp-1R was significantly lower in refed rats compared with food-restricted rats. The measures of gene expression in two feeding control groups (ad libitum and voluntarily overfed animals) were Intermediate between the food-restricted and refed groups, but were not significantly different from each other. The results indicate that putative glucosensing (GK, Glut-2, and Glp-1R) gene expression in the hypothalamus and brainstem is reduced in response to food Intake, depending on prior nutritional status.