title: Regional distribution of SGLT activity in rat brain in vivo.
abstract: Na(+)-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[(18)F]fluoro-D-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood-brain barrier (BBB), in vivo delivery of the probe into the brain was achieved after opening of the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum, hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex, and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia prompt the speculation that SGLTs may play an essential role in glucose utilization under stress such as ischemia. The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes.
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Yu
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hirayama
authors.forename: Gerald
authors.initials: G
authors.lastname: Timbol
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.forename: Ana
authors.initials: A
authors.lastname: Diez-Sampedro
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kepe
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: Sung-Cheng
authors.initials: SC
authors.lastname: Huang
authors.forename: Ernest M
authors.initials: EM
authors.lastname: Wright
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Barrio
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D011877:Radionuclide Imaging; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; C495676:Slc5a1 protein, rat; D051269:Sodium-Glucose Transporter 1