Shuttling glucose across brain microvessels, with a little help from GLUT1 and AMP kinase. Focus on “AMP kinase regulation of sugar transport in brain capillary endothelial cells during acute metabolic stress”

Abstract

The Blood-Brain Barrier: a Gatekeeper of Brain “Individuality” The blood-brain barrier (BBB) maintains the individuality of brain fluid, while allowing it to selectively import nutrients and process toxic products. Its major constituent is a single layer of continuous, nonfenestrated endothelium lining the microvessels, whose unique features account in large part for the integrity of the barrier. The endothelial cell monolayer is the major determinant, but other cells in the central nervous system (e.g., pericytes and astrocytes) contribute to the integrity of the BBB. The interendothelial tight junctions of the BBB are one of its signature elements that greatly restrict paracellular permeability to solutes, fluid, and transmigrating cells. This is markedly distinct from the leakier, discontinuous, and fenestrated endothelium of liver microvessels (sinusoids). For example, the tight junctions of the cerebral endothelium (pial vessels) confer an electrical resistance (1,300 ·cm 2 ) far higher than other endothelia (6). Therefore, communication between blood and the brain interstitial fluid requires individually tailored molecular mechanisms. Transcytosis is the movement of molecules through a cellular barrier. Whereas proteins can traverse through vesicular carrier processes that could carry solutes through fluid phase endocytosis, the brain microvasculature is uniquely poor in plasmalemmal and cytoplasmic caveolae (1). Instead, bidirectional passage of small molecules across the BBB is stringently regulated by numerous transporters and receptors. These typically work in tandem across the luminal and abluminal membranes of the endothelial cell.