Blood-brain glucose transfer in diabetes mellitus: Decreased number of glucose transporters at blood-brain barrier

Abstract

This study describes the effects of streptozocin (STZ)-induced diabetes mellitus on the glucose-transporter system of the rat blood-brain barrier. Subcellular membrane fractions, i.e., plasma membrane and high- and low-density microsomes, were prepared from isolated brain microvessels derived from control and diabetic animals. The number of glucose transporters in each of the membrane fractions from both control and diabetic animals was determined by the D-glucose-inhibitable cytochalasin B-binding assay. The total number of glucose transporters was decreased by 43% in STZ-treated rats compared with controls (35 vs. 115 pmol/mg protein; P < .05). The glucose-transporter number in plasma membranes was decreased by 50%, in high-density microsomes by 38%, and in low-density microsomes by 45%. Incubation of isolated microvessels from control animals with 7 μM insulin for 30 min at 37°C led to a cytoheximide-sensitive 27% increase (P < .05) in the number of transporters in high-density microsomes. This insulin effect was significantly diminished to 15% in the diabetic animals (P < .05). In conclusion, 1) STZ-induced diabetes decreases the glucose-transporter number in all subcellular membrane fractions derived from isolated rat brain microvessels, and 2) the insulin-induced increase in de novo synthesis of glucose transporters in brain microvessles is diminished in these chronically diabetic animals.