Downregulation of blood-brain barrier glucose transporter in experimental diabetes

Luminal and abluminal endothelial plasma membrane vesicles were isolated from bovine cerebral microvessels, the site of the blood-brain barrier. Glucose transport across each membrane was measured using a rapid-filtration technique. Glucose transport into luminal vesicles occurred by a stereospecific energy-independent transporter [Michaelis-Menten constant (K(m)) = 10.3 +/- 2.8 (SE) mM and maximal velocity (Vmax) = 8.6 +/- 2.0 nmol.mg protein(-1).min-1]. Kinetic analysis of abluminal vesicles also showed a transport system with characteristics similar to the luminal transporter (K(m) = 12.5 +/- 2.3 mM and Vmax = 10.0 +/- 1.0 nmol.mg protein-1.min-1). These functional, facilitative glucose transporters were symmetrically distributed between the luminal and abluminal membrane domains, providing a mechanism for glucose movement between blood and brain. The studies also revealed a Na-dependent transporter on the abluminal membrane with a higher affinity and lower capacity than the facilitative transporters (K(m) = 130 +/- 20 microM and Vmax = 1.59 +/- 0.44 nmol.mg protein-1.min-1. The abluminal Na-dependent glucose transporter is in a position to transport glucose from the brain extracellular fluid into the endothelial cells of the blood-brain barrier. The functional significance of its presence there remains to be determined.

Download Full-text

Molecular regulation of the blood-brain barrier GLUT1 glucose transporter by brain-derived peptides

Journal of Neural Transmission Supplement - New Trends in the Diagnosis and Therapy of Non-Alzheimer’s Dementia ◽

10.1007/978-3-7091-6892-9_20 ◽

1996 ◽

pp. 275-275 ◽

Cited By ~ 1

Author(s):

R. J. Boado

Keyword(s):

Blood Brain Barrier ◽

Glucose Transporter ◽

Molecular Regulation ◽

Brain Barrier ◽

Blood Brain ◽

Glut1 Glucose Transporter

Download Full-text

Glucose Transporter of the Blood-Brain Barrier and Brain in Chronic Hyperglycemia

Journal of Neurochemistry ◽

10.1111/j.1471-4159.1988.tb01180.x ◽

1988 ◽

Vol 51 (6) ◽

pp. 1930-1934 ◽

Cited By ~ 38

Author(s):

Sami I. Harik ◽

Stephen A. Gravina ◽

Rajesh N. Kalaria

Keyword(s):

Blood Brain Barrier ◽

Glucose Transporter ◽

Brain Barrier ◽

Chronic Hyperglycemia ◽

Blood Brain

Download Full-text

Blood-Brain Barrier Transport and Brain Metabolism of Glucose during Acute Hyperglycemia in Humans1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.5.7490 ◽

2001 ◽

Vol 86 (5) ◽

pp. 1986-1990

Author(s):

Steen G. Hasselbalch ◽

Gitte M. Knudsen ◽

Brunella Capaldo ◽

Alfredo Postiglione ◽

Olaf B. Paulson

Keyword(s):

Blood Brain Barrier ◽

Glucose Transporter ◽

Human Subjects ◽

Brain Barrier ◽

Indicator Method ◽

Acute Hyperglycemia ◽

Blood Brain ◽

18F Fluorodeoxyglucose ◽

Positron Emission ◽

Area Product

It is controversial whether transport adaptation takes place in chronic or acute hyperglycemia. Blood-brain barrier glucose permeability and regional brain glucose metabolism (CMRglc) was studied in acute hyperglycemia in six normal human subjects (mean age, 23 yr) using the double indicator method and positron emission tomography and[ 18F]fluorodeoxyglucose as tracer. The Kety-Schmidt technique was used for measurement of cerebral blood flow (CBF). After 2 h of hyperglycemia (15.7 ± 0.7 mmol/L), the glucose permeability-surface area product from blood to brain remained unchanged (0.050 ± 0.008 vs. 0.059 ± 0.031 mL/100 g·min). The unidirectional clearance of[ 18F]fluorodeoxyglucose (K1*) was reduced from 0.108 ± 0.011 to 0.061 ± 0.005 mL/100 g·min (P < 0.0004). During hyperglycemia, global CMRglc remained constant (21.4 ± 1.2 vs. 23.1 ± 2.2 μmol/100 g·min, normo- and hyperglycemia, respectively). Except for a significant increase in white matter CMRglc, no regional difference in CMRglc was found. Likewise, CBF remained unchanged. The reduction in K1* was compatible with Michaelis-Menten kinetics for facilitated transport. Our findings indicate no major adaptational changes in the maximal transport velocity or affinity to the blood-brain barrier glucose transporter. Finally, hyperglycemia did not change global CBF or CMRglc.

Download Full-text