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Insulin receptors in the brain: structural and physiological characterization.
M K Raizada1, J Shemer, J H Judkins
1Department of Physiology, University of Florida College of Medicine, Gainesville 32610.
Neurochemical Research
|April 1, 1988
Summary
This study found specific insulin receptors in adult rat brain synaptosomes. Insulin inhibits norepinephrine uptake by reducing active uptake sites, highlighting its role in brain neurotransmission.
Area of Science:
- Neuroscience
- Endocrinology
- Molecular Biology
Background:
- Insulin's role in the brain is increasingly recognized, extending beyond glucose metabolism.
- Insulin receptors are present in the brain, but their function in neuronal preparations like synaptosomes requires further characterization.
Purpose of the Study:
- To characterize insulin receptors in adult rat brain synaptosomes.
- To investigate the functional effects of insulin on neurotransmitter uptake in these synaptosomes.
Main Methods:
- Binding assays using 125I-insulin to quantify receptor characteristics.
- Cross-linking studies followed by SDS-PAGE to determine receptor subunit molecular weights.
- Insulin-stimulated phosphorylation assays.
- Measurement of [3H]norepinephrine uptake in response to insulin.
Main Results:
- Specific, time-dependent binding of 125I-insulin to synaptosome receptors was observed.
- The alpha subunit of the brain insulin receptor (122,000 MW) was smaller than the liver counterpart.
- Insulin stimulated phosphorylation of a 95,000 MW protein, identified as the beta subunit.
- Insulin dose-dependently inhibited norepinephrine uptake by decreasing active uptake sites.
Conclusions:
- Adult rat brain synaptosomes possess specific insulin receptors.
- Insulin exerts inhibitory effects on norepinephrine uptake in the brain synaptosome preparation.
- These findings suggest a role for insulin in modulating neurotransmission in the central nervous system.