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The source of cerebral insulin
1Research Service (151), GRECC, Veterans Affairs Medical Center-St. Louis and Saint Louis University School of Medicine, Division of Geriatrics, Department of Internal Medicine, WAB, 915 N. Grand Boulevard, St. Louis, MO 63106, USA. bankswa@slu.edu
European Journal of Pharmacology
|April 20, 2004
Summary
Peripheral insulin crosses the blood-brain barrier (BBB) via a saturable transporter, enabling its action within the central nervous system (CNS). This transport is regulated and influenced by various physiological states and diseases.
Area of Science:
- Neuroendocrinology
- Molecular Biology
- Physiology
Background:
- Insulin receptors are present in the central nervous system (CNS), but endogenous CNS insulin production is minimal.
- Peripheral insulin must cross the blood-brain barrier (BBB) to exert effects within the CNS.
Purpose of the Study:
- To investigate the mechanism and regulation of insulin transport across the BBB.
- To understand the physiological significance of CNS insulin in relation to peripheral insulin.
Main Methods:
- Characterization of the saturable transport mechanism for insulin across the BBB.
- Analysis of insulin transporter distribution and saturation kinetics within the CNS.
- Review of factors affecting BBB insulin transport.
Main Results:
- Insulin crosses the BBB via a saturable, unevenly distributed transporter, with olfactory bulbs showing the highest transport rate.
- The transporter is partially saturated at euglycemic levels, suggesting signaling at physiological blood insulin concentrations.
- Insulin transport is modulated by development, fasting, obesity, hibernation, diabetes mellitus, and Alzheimer's disease.
Conclusions:
- BBB insulin transport is a key mechanism for peripheral insulin to act as a regulatory peptide in the CNS.
- Dysregulation of this transport may underlie conditions like insulin resistance and altered appetite.
- Insulin also influences BBB functions, indicating a complex interplay.