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Updated: Aug 14, 2026

Hyperinsulinemic-Euglycemic Clamp in the Conscious Rat
Published on: February 8, 2011
Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat
Insights
Researchers found that the brain actively takes up insulin from cerebrospinal fluid (CSF). This brain insulin uptake is crucial for insulin
Area of Science:
- Neuroscience
- Endocrinology
Background:
- Insulin plays a role in brain function.
- The mechanism of insulin transport into the brain from cerebrospinal fluid (CSF) is not fully understood.
Purpose of the Study:
- To investigate the uptake and distribution of insulin within the brain from the CSF.
- To determine if insulin uptake from the CSF is an active and specific process.
Main Methods:
- Infusion of tracer doses of 125I-(Tyr A14)-insulin into the CSF of animal models.
- Measurement of labeled insulin concentration in CSF over time.
- Comparison of labeled insulin clearance with 3H-inulin, a marker of CSF bulk flow.
- Assessment of the effect of co-infusion with unlabeled insulin or ribonuclease B on labeled insulin uptake and degradation.
Main Results:
- Labeled insulin showed a slow increase in CSF, reaching a plateau after 2 hours.
- Insulin was cleared from CSF faster than 3H-inulin, suggesting active transport.
- The majority of labeled insulin distributed to ventricular and periventricular brain regions.
- Degraded insulin was detected in CSF.
- Excess unlabeled insulin impaired insulin clearance and degradation, and reduced brain labeling in specific regions (medial hypothalamus, olfactory bulbs, brain stem).
- Ribonuclease B did not affect insulin uptake, indicating specificity.
Conclusions:
- There is an active, specific uptake of insulin from the CSF into distinct brain compartments.
- This active insulin transport from CSF into the brain is likely essential for insulin's effects on brain function.
Abstract:
Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function.

