There is increasing evidence that in the kidney and small intestine, expression levels of the facilitative glucose transporters are influenced by changes in plasma glucose concentrations. Indeed, our previous studies have reported increased GLUT2 expression at the proximal tubule brush border membrane (BBM) of animals with streptozotocin (STZ)-induced Type 1 diabetes. Overnight fasting of these animals normalised plasma glucose levels and abolished the increased GLUT2 expression (Marks et al. 2003). In the present study, we aimed to determine if more subtle changes in plasma glucose concentration may also influence GLUT2 expression at the BBM. Administration of nicotinamide to STZ-injected animals has been shown to partially abolish the diabetogenic effect of STZ and moderate the degree of hyperglycaemia (Masiello et al. 1998). Therefore, we adjusted plasma glucose concentrations in STZ-injected animals by using increasing doses of nicotinamide and measured GLUT2 expression at the BBM. Male Sprague-Dawley rats (250g) received a single i.p. injection of nicotinamide (0, 50, 150 or 200mg/kg) followed by a single tail vein injection of STZ (60mg/kg) 15 min later, administered under light isoflurane anaesthesia. After 2 weeks, rats were terminally anaesthetised, the kidneys removed and the cortex dissected away. BBM vesicles were then prepared at 4°C using the two-stage magnesium precipitation method and GLUT2 expression levels (normalised to β-actin) were established using a standard Western blot protocol. All statistical analyses were performed using ANOVA. Animals receiving only STZ showed a 2.8-fold increase in plasma glucose concentration (C: 12.1 ± 0.35 vs. STZ: 34.3 ± 1.76 mmol/l, n=6, P<0.001) and a 2.9-fold increase in GLUT2 expression (C: 100% vs. STZ: 292 ± 29%, n=6, P<0.001). Low dose nicotinamide (50mg/kg) reduced plasma glucose levels to 1.85-fold (22.4 ± 3 mmol/l, n=6, P<0.01) and depressed GLUT2 expression to 1.9-fold (192 ± 22%, n=6, P<0.05) of the control values. High dose nicotinamide (200mg/kg) normalised blood glucose (12.4 ± 0.41 mmol/l, n=6) and GLUT2 expression (115 ± 16%, n=6) to levels similar to those found in control animals. Analysis of the results showed a strong correlation (R² = 0.91) between plasma glucose concentration and GLUT2 expression at the BBM. We conclude that GLUT2 expression at the proximal tubule BBM is highly dependent on glycaemic status.