Cited by 184Barrier Structure and Function StudiesDrug Transport and Resistance MechanismsIon Transport and Channel Regulation

Downregulation of Blood-Brain Barrier Glucose Transporter in Experimental Diabetes

Pardridge, William M, Triguero, Domingo, Farrell, Christine R·1990·Diabetes

Abstract

Previous studies showing downregulation of bloodbrain barrier (BBB) glucose-transporter activity in vivo in experimental diabetes have recently been questioned. Therefore, our investigations examined both the BBB glucose-transporter activity in experimental diabetes in vivo, with the use of the in situ internal carotid artery perfusion technique, and the microvessel glucose-transporter concentration, with quantitative Western immunoblots. These studies show that BBB glucose-transporter activity in vivo is decreased 44% in experimental diabetes (blood glucose concn 443 ± 12 mg/dl), parallel with a 44% decrease in cerebral blood flow, a normal brain blood volume, and a 75% prolongation of capillary transit time. The glucose-transporter concentration is decreased 77 ± 9% in microvessels isolated from diabetic rat brain compared with controls, as measured by quantitative Western blotting. These studies confirm the original observations that the BBB glucose transporter is downregulated in experimental diabetes, in association with a parallel decrease in cerebral blood flow. In addition, these studies, in conjunction with other recent experiments from this laboratory showing elevated glucose-transporter mRNA in diabetic rat brain capillaries, suggest the primary mechanism underlying the downregulation is a posttranscriptional inhibition of glucose-transporter mRNA translation.

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Crossref · 10.2337/diab.39.9.1040

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Authors
Pardridge, W. M., Triguero, D., & Farrell, C. R.
Affiliations
University of California, Los Angeles (US)
Venue
Diabetes
Published
1990-09-01
Volume
39
Issue
9
Pages
1040-1044
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
OpenAlex
W1967064176
Cited by
184
References
33
Citations by year
2026: 1 · 2025: 3 · 2024: 2 · 2023: 5 · 2022: 8 · 2021: 4 · 2020: 6 · 2019: 6 · 2018: 8 · 2017: 4 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 1 · 2012: 4
FWCI
5.78
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R01-NS-25554)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
blood-brain barrier, glucose transporters, experimental diabetes, cerebral blood flow, capillary transit time, brain capillaries, post-transcriptional regulation
MeSH terms
Animals, Blood Glucose, Blood-Brain Barrier, Brain, Capillary Permeability, Cerebrovascular Circulation, Diabetes Mellitus, Experimental, Glucose, RNA Processing, Post-Transcriptional, RNA, Messenger, Rats

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