ABSTRACT
Immunoreactivity of the Na+-D-glucose cotransporter SGLT1 was demonstrated in intracerebral capillaries of rat and pig. Immunostaining suggested that SGLT1 is located in the luminal membrane of the endothelial cells and in intracellular vesicles. Using in situ hybridization, SGLT1 mRNA was not detectable in intracerebral capillaries of non-treated or sham-operated Wistar rats. However, 1 day after a transient occlusion of the right middle cerebral artery, SGLT1 mRNA was detected in capillaries of both brain hemispheres. Expression of SGLT1 was also demonstrated in primary cultures of capillary endothelial cells from pig using polymerase chain reaction after reverse transcription and western blotting. The data suggest that SGLT1 participates in transport of D-glucose across the blood-brain barrier and is upregulated after brain ischemia and reperfusion.
Subject(s)
Blood-Brain Barrier/metabolism , Endothelial Cells/metabolism , Glucose/metabolism , Membrane Glycoproteins/metabolism , Monosaccharide Transport Proteins/metabolism , Up-Regulation , Animals , Cells, Cultured , Immunohistochemistry , Male , Rats , Rats, Wistar , Sodium-Glucose Transporter 1 , SwineABSTRACT
By immunohistochemistry, we demonstrated the localization of the Na(+)-D-glucose cotransporter SGLT1 in capillaries of rat heart and skeletal muscle, but not in capillaries of small intestine and submandibular gland. mRNA of SGLT1 was identified in skeletal muscle and primary cultured coronary endothelial cells. The functional relevance of SGLT1 for glucose transport across capillary walls in muscle was tested by measuring the extraction of D-glucose from the perfusate during non-recirculating perfusion of isolated rat hindlimbs. In this model, D-glucose extraction from the perfusate is increased by insulin which accelerates D-glucose uptake into myocytes by increasing the concentration of glucose transporter GLUT4 in the plasma membrane. The insulin-induced increase of D-glucose extraction from the perfusate was abolished after blocking SGLT1 with the specific inhibitor phlorizin. The data show that SGLT1 in capillaries of skeletal muscle is required for the action of insulin on D-glucose supply of myocytes.
