Steady-state levels of the major glucose transporter gene (GLUT-1) of the brain were evaluated under three conditions that induced chronic changes in plasma glucose and insulin in adult rats: (i) repeated injection of insulin for 5 days, resulting in plasma glucose levels of 60-70 mg/dl for at least 3 days; (ii) fasting for 3 days; and (iii) moderate streptozotocin-induced diabetes of 1 week duration. Brain GLUT-1 mRNA was measured by dot blot hybridization with a HepG2/erythrocyte (GLUT1) [(32)P]cRNA probe, and GLUT-1 protein by immunoblot analysis with a polyclonal antibody (11493). Insulin injection resulted in hypoglycemia, increased GLUT-1 mRNA (143 +/- 15%, P < 0.05), and increased GLUT-1 protein (141 +/- 6%, P < 0.05). The increase in GLUT-1 mRNA was specific for brain, as no change was observed in liver or kidney. Fasting resulted in mild hypoglycemia, lower plasma insulin, increased GLUT-1 mRNA (131 +/- 17%, P < 0.05 vs control), and no change in GLUT-1 protein (125 +/- 9%, N.S.). Mild streptozotocin diabetes resulted in hyperglycemia, undetectable plasma insulin, decreased GLUT-1 mRNA (65 +/- 6%, P < 0.05 vs control), and no change in GLUT-1 protein (84 +/- 9%, N.S.). A negative correlation (r = -0.61, P < .0001) between GLUT-1 mRNA levels in brain and plasma glucose concentrations was observed among the three experimental groups and control animals, suggesting that the plasma glucose concentration may be at least one determinant of GLUT-1 levels in rat brain. The importance of these results is the finding that GLUT-1 gene expression in rat brain is regulated in vivo by the nutritional and endocrine status of the animal.