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Cited by 126Ion Transport and Channel RegulationBarrier Structure and Function StudiesDrug Transport and Resistance Mechanisms

Regional distribution of SGLT activity in rat brain in vivo

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Yu, Amy S., Hirayama, Bruce A., Timbol, Gerald, Liu, Jie, Diez-Sampedro, Ana, Kepe, Vladimir, Satyamurthy, Nagichettiar, Huang, Sung-Cheng +2 more·2013·American Journal of Physiology-Cell Physiology
DOI 10.1152/ajpcell.00317.2012PMC PMC3566441
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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.

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  • SGLT1 is found in neurons.

    “Endothelial cells also express sodium glucose cotransporter 1 (SGLT1) (159) that is found in neurons (671), but its physiological role in glucose transport across the BBB remains elusive.”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [671]

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Authors
Yu, A. S., Hirayama, B. A., Timbol, G., Liu, J., Diez-Sampedro, A., Kepe, V., Satyamurthy, N., Huang, S.-C., Wright, E. M., & Barrio, J. R.
Affiliations
  • University of California, Los Angeles (US)
  • Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, California
Corresponding author
  • Wright, Ernest M.
  • Barrio, Jorge R.
ORCID
Venue
American Journal of Physiology-Cell Physiology
Publisher
American Physiological Society
Published
2013-02-01
Volume
304
Issue
3
Pages
C240-C247
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
DOI
10.1152/ajpcell.00317.2012
PMC
PMC3566441
OpenAlex
W2140454350
Cited by
126
References
2
Citations by year
2026: 11 · 2025: 13 · 2024: 9 · 2023: 6 · 2022: 14 · 2021: 11 · 2020: 17 · 2019: 3 · 2018: 13 · 2017: 10 · 2016: 7 · 2015: 5 · 2014: 6 · 2013: 1
FWCI
1.54
Type
journal article
Language
en
Open access
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (P01AG025831)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK-019567, R01DK077133, R01DK019567)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
sodium-glucose cotransporter, Na+/glucose cotransporter, SGLT1, brain, regional distribution, blood-brain barrier, osmotic shock, cerebellum, hippocampus, cerebral cortex, caudate nucleus, putamen, amygdala, paraventricular nucleus, brainstem, glucose utilization, anoxia, ischemia, SGLT inhibitors, diabetes mellitus
MeSH terms
Animals, Autoradiography, Biological Transport, Blood-Brain Barrier, Brain, Female, Immunohistochemistry, Radionuclide Imaging, RNA, Messenger, Tissue Distribution, Rats, Sprague-Dawley, Sodium-Glucose Transporter 1, Glucose Transporter Type 1, Rats

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