The source of cerebral insulin
Abstract
Insulin and its receptor are found throughout the central nervous system (CNS). Insulin administered into the CNS can exert powerful effects, yet the consensus is that little or no insulin is produced in the CNS. Therefore, CNS insulin is essentially dependent on the ability of peripheral insulin to cross the blood-brain barrier (BBB). Insulin is known to cross the BBB by a saturable transport mechanism. This transporter shows some thematic similarities to other transporters for peptides or regulatory proteins. It is unevenly distributed throughout the CNS with the olfactory bulbs having the fastest transport rate of any brain region. It is partially saturated at euglycemic levels, suggesting that its main signaling function occurs at physiological blood levels, rather than as a brake to hypoglycemic events. One probable function of the BBB transporter is to allow CNS insulin to act as a counter-regulatory hormone to peripheral insulin. The transporter is regulated, with the transport rate of insulin being altered during development and by fasting, obesity, hibernation, diabetes mellitus and Alzheimer's disease. Enhancement of insulin transport by lipopolysaccharide could be the basis for the insulin resistance seen with bacterial infections. Inhibition of insulin transport across the BBB by dexamethasone could be the basis for the enhanced appetite seen with glucocorticoid treatments. Insulin itself also has effects on the BBB, altering enzymatic and transporter functions. Overall, BBB transport of insulin provides a mechanism for peripheral insulin to act within the CNS as a regulatory peptide.
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Central insulin is a hormonal signal that provides negative feedback to the brain for the regulation of glucose homeostasis.
“Central insulin is also a hormonal signal that provides negative feedback to the brain for the regulation of glucose homeostasis [16].”
From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [16]
The framework corresponding to feedback control of brain glucose homeostasis is supported by anatomical evidence.
“Such a framework corresponding to feedback control of brain glucose homeostasis is supported by anatomical evidences.”
From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [16]
Insulin transport across the blood-brain barrier / blood-CSF barrier is characterized by saturation.
“However, such transport is characterized by saturation [16].”
From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [16]
Hyperglycemia abolishes insulin transport across the blood-brain barrier.
“Furthermore, hyperglycemia abolishes insulin transport across BBB [16].”
From A mathematical model of brain glucose homeostasis (2009) · cites this paper as [16]
The blood-brain barrier is passively permeable to molecules smaller than 400 Da with fewer than eight to 10 hydrogen bonds and enables active, often saturable transport of bigger molecules.
“The BBB is passively permeable to molecules < 400 Da in size and with fewer than eight to 10 hydrogen bonds and enables the active, often saturable transport of bigger molecules.”
From Intranasal insulin (2021) · cites this paper as [17]
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- Authors
- Banks, W. A.
- Affiliations
- St. Louis VA Medical Center (US)
- Corresponding author
- Banks, William A.
- ORCID
- Banks, William A.
- Venue
- European Journal of Pharmacology
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 490
- Issue
- 1-3
- Pages
- 5-12
- ISSN
- 0014-2999 (ISSN-L)
- OpenAlex
- W1965600418
- Cited by
- 489
- References
- 83
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 14 · 2023: 15 · 2022: 26 · 2021: 27 · 2020: 22 · 2019: 26 · 2018: 18 · 2017: 23 · 2016: 29 · 2015: 30 · 2014: 33 · 2013: 23 · 2012: 30
- FWCI
- 12.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Pharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- insulin receptor, blood-brain barrier, insulin transport, olfactory bulb, insulin resistance, lipopolysaccharide, dexamethasone, glucocorticoids, appetite, diabetes mellitus, Alzheimer's disease, fasting, obesity, hibernation, brain development
- MeSH terms
- Animals, Biological Transport, Blood-Brain Barrier, Central Nervous System, Humans, Insulin
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