DOWN-REGULATION OF BLOOD-BRAIN GLUCOSE-TRANSPORT IN THE HYPERGLYCEMICNONOBESE DIABETIC MOUSE

The intracarotid injection method has been utilized to examine blood-b rain barrier (BBB) glucose transport in hyperglycemic (4-6 days) mice. In anesthetized mice, Brain Uptake Indices were measured over a range of glucose concentrations from 0.010-50 mmol/l; glucose uptake was fo und to be saturable and kinetically characterized. The maximal velocit y (V-max) for glucose transport was 989 +/- 214 nmol . min(-1). g(-1). and the half-saturation constant estimated to be 5.80 +/- 1.38 mmol/l . The unsaturated Permeability Surface area product (PS) is = 171 + 8 mu l . min.(-1). g-(1) . A rabbit polyclonal antiserum to a synthetic peptide encoding the 13 C-terminal amino acids of the human erythrocyt e glucose transporter immunocytochemically confirmed the presence of t he GLUT1 isoform in non-obese diabetic (NOD) mouse brain capillary end othelia. These studies indicate that a down-regulation of BBB glucose transport occurs in these spontaneously hyperglycemic mice; both BBB g lucose permeability (as indicated by PS product) and transporter maxim al velocity are reduced (in comparison to normoglycemic CD-1 mice), bu t the half-saturation constant remains unchanged.