Two brain regions - the basomedial hypothalamus and area postrema (AP) - react to changes in circulating glucose levels by altering feeding behavior and the secretion of pituitary and non-pituitary hormones. The precise identity of cells responding to glucose in these regions is uncertain. The recent detection of high-capacity glucose transporter proteins in astrocytes in these areas has suggested that astrocytes may play a role in glucose sensing by the brain. To test this hypothesis, rats were injected with either saline or methionine sulfoximine (MS), a compound that produces alterations in carbohydrate and glutamate metabolism in astrocytes. Eighteen hours later, rats were injected with either saline or 2-deoxy glucose (2-DG) and brain sections were stained to demonstrate 2-DG-activated neurons immunoreactive for Fos protein. MS-treated rats showed a 70% reduction in numbers of Fos+ neurons in the AP region (p<0.05). Also, specialized, Gomori+ astrocytes were particularly abundant in both glucose sensitive regions and showed a distribution identical to that reported for high-capacity glucose transporter proteins. These data suggest that specialized astrocytes influence the glucose-sensing function of the brain.