Expression of the Na+-D-glucose cotransporter SGLT1 in neurons.
In brains of the rabbit, pig, and human, expression of the high-affinity Na+-D-glucose cotransporter SGLT1 and of the protein RS1, which alters the activity of SGLT1, was demonstrated. In situ hybridization showed that SGLT1 and RS1 are transcribed in pyramidal cells of brain cortex and hippocampus and in Purkinje cells of cerebellum. In neurons of pig brain SGLT1 protein was demonstrated by western blotting with synaptosomal membranes and by immunohistochemistry, which showed SGLT1 in pyramidal and Purkinje cells. To test whether SGLT1 in neurons may be activated during increased D-glucose consumption, an epileptic seizure was induced in rat brain, and the uptake of specific nonmetabolized substrates of SGLT1 [[14C]methyl-alpha-D-glucopyranoside ([14C]AMG)] and of Na+-independent transporters [2-deoxy-D-[14C] glucose ([14C]2-DG)] was analyzed by autoradiography. During the seizure the uptake of AMG and 2-DG was increased in the focus. Within two hours after the seizure 2-DG uptake in the focus returned to normal. In contrast, the AMG uptake in the focus area was still increased 1 day later. The data show that the high-affinity Na+-D-glucose cotransporter SGLT1 is expressed in neurons and can be up-regulated.
Poppe
R
R
Anatomisches Institut, Bayerische Julius-Maximilians-Universität, Würzburg, Germany.
Karbach
U
U
Gambaryan
S
S
Wiesinger
H
H
Lutzenburg
M
M
Kraemer
M
M
Witte
O W
OW
Koepsell
H
H
D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry / Q000502:physiology*; D002250:Carbon Radioisotopes; D018076:DNA, Complementary / Q000032:analysis / Q000302:isolation & purification; D003847:Deoxyglucose; D004285:Dogs; D004827:Epilepsy / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D009457:Neuroglia / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D011817:Rabbits; D051381:Rats; D017422:Sequence Analysis, DNA; D012964:Sodium / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1; D013552:Swine; D014158:Transcription, Genetic / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D002250:Carbon Radioisotopes; D018076:DNA, Complementary; D008562:Membrane Glycoproteins; D009004:Monosaccharide Transport Proteins; C495674:SLC5A1 protein, human; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1; D003847:Deoxyglucose; D012964:Sodium; D005947:Glucose