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Regional Distribution of SGLT Activity in Rat Brain In vivo.
MedLine Citation:
PMID:  23151803     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Na/glucose cotransporter 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 the physiological significance remains elusive. In this work we mapped in vivo the regional distribution of functional SGLTs in rat brain using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[F-18]fluoro-D-glucopyranoside (Me-4FDG) with ex vivo autoradiography, and immunohistochemistry. Since Me-4FDG 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 the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4FDG 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-4FDG accumulated in the brainstem. The regional accumulation of Me-4FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after opening the BBB, the specific substrate for SGLTs, Me-4FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia, prompts 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     Date:  2012-11-14
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  -     ISSN:  1522-1563     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
David Geffen School of Medicine, University of California Los Angeles.
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