Document Detail


Regional distribution of SGLT activity in rat brain in vivo.
MedLine Citation:
PMID:  23151803     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Amy S Yu; Bruce A Hirayama; Gerald Timbol; Jie Liu; Ana Diez-Sampedro; Vladimir Kepe; Nagichettiar Satyamurthy; Sung-Cheng Huang; Ernest M Wright; Jorge R Barrio
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-11-14
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  304     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-06-10     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C240-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Autoradiography / methods
Biological Transport
Blood-Brain Barrier / metabolism
Brain / metabolism*,  radionuclide imaging
Female
Glucose Transporter Type 1 / genetics,  metabolism
Immunohistochemistry / methods
RNA, Messenger / genetics
Rats
Rats, Sprague-Dawley
Sodium-Glucose Transporter 1 / genetics,  metabolism*
Tissue Distribution
Grant Support
ID/Acronym/Agency:
DK-019567/DK/NIDDK NIH HHS; P01 AG-025831/AG/NIA NIH HHS; R01 DK-077133/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Glucose Transporter Type 1; 0/RNA, Messenger; 0/Slc2a1 protein, rat; 0/Slc5a1 protein, rat; 0/Sodium-Glucose Transporter 1
Comments/Corrections

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