Cited by 183Cerebrospinal fluid and hydrocephalusBarrier Structure and Function StudiesIon Transport and Channel Regulation

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Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport.

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Schwartz, M W, Bergman, R N, Kahn, S E, Taborsky, G J, Fisher, L D, Sipols, A J, Woods, S C, Steil, G M, Porte, D·1991·Journal of Clinical Investigation

DOI 10.1172/jci115431PMC PMC295596

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Abstract

To study the route by which plasma insulin enters cerebrospinal fluid (CSF), the kinetics of uptake from plasma into cisternal CSF of both insulin and [14C]inulin were analyzed during intravenous infusion in anesthetized dogs. Four different mathematical models were used: three based on a two-compartment system (transport directly across the blood-CSF barrier by nonsaturable, saturable, or a combination of both mechanisms) and a fourth based on three compartments (uptake via an intermediate compartment). The kinetics of CSF uptake of [14C]inulin infused according to an "impulse" protocol were accurately accounted for only by the nonsaturable two-compartment model (determination coefficient [R2] = 0.879 +/- 0.044; mean +/- SEM; n = 5), consistent with uptake via diffusion across the blood-CSF barrier. When the same infusion protocol and model were used to analyze the kinetics of insulin uptake, the data fit (R2 = 0.671 +/- 0.037; n = 10) was significantly worse than that obtained with [14C]inulin (P = 0.02). Addition of a saturable component of uptake to the two-compartment model improved this fit, but was clearly inadequate for a subset of insulin infusion studies. In contrast, the three-compartment model accurately accounted for CSF insulin uptake in each study, regardless of infusion protocol (impulse infusion R2 = 0.947 +/- 0.026; n = 10; P less than 0.0001 vs. each two-compartment model; sustained infusion R2 = 0.981 +/- 0.003; n = 5). Thus, a model in which insulin passes through an intermediate compartment en route from plasma to CSF, as a part of a specialized transport system for the delivery of insulin to the brain, best accounts for the dynamics of this uptake process. This intermediate compartment could reside within the blood-CSF barrier or it may represent brain interstitial fluid, if CNS insulin uptake occurs preferentially across the blood-brain barrier.

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Authors: Schwartz, M. W., Bergman, R. N., Kahn, S. E., Taborsky, G. J., Fisher, L. D., Sipols, A. J., Woods, S. C., Steil, G. M., & Porte, D.
Affiliations: University of Washington (US)
University of Southern California (US)
United States Department of Veterans Affairs (US)
ORCID: Bergman, R N
Kahn, S E
Woods, S C
Steil, G M
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1991-10-01
Volume: 88
Issue: 4
Pages: 1272-1281
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci115431
PMC: PMC295596
OpenAlex: W1967708672
Cited by: 183
References: 27
Citations by year: 2026: 1 · 2025: 1 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 5 · 2016: 4 · 2015: 5 · 2014: 3 · 2013: 6 · 2012: 5
FWCI: 1.57
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Department of Veterans Affairs
National Institutes of Health (1f32dk008025-01, 2r01dk012829-36)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, DK-17047, DK-08025, P30DK017047)
Topics: Health Sciences › Medicine › Clinical Neurology › Cerebrospinal fluid and hydrocephalus
Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords: insulin, cerebrospinal fluid, blood-CSF barrier, intermediate compartment, inulin, two-compartment model, three-compartment model, saturable transport, blood-brain barrier
MeSH terms: Animals, Biological Transport, Blood-Brain Barrier, Dogs, Infusions, Intravenous, Insulin, Inulin, Male, Models, Biological

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Evidence for entry of plasma insulin into cerebrospinal fluid through an intermediate compartment in dogs. Quantitative aspects and implications for transport.

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