Insulin receptors in the brain: Structural and physiological characterization

Mohan K. Raizada*, J. Shemer, Jennifer H. Judkins, Derrel W. Clarke, Brian A. Masters, Derek LeRoith

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

The present study was conducted to characterize insulin receptors and to determine the effects of insulin in synaptosomes prepared from adult rat brains. Binding of125I-insulin to synaptosome insulin receptors was highly specific and time dependent: equilibrium binding was obtained within 60 minutes, and a t1/2 of dissociation of 26 minutes. Cross-linking of125I-insulin to its receptor followed by SDS-PAGE demonstrated that the apparent molecular weight of the alpha subunit of the receptor was 122,000 compared with 134,000 for the liver insulin receptor. In addition, insulin stimulated the dose-dependent phosphorylation of exogenous tyrosine containing substrate and a 95,000 MW plasma membrane associated protein, in a lectin-purified insulin receptor preparation. The membrane associated protein was determined to be the β subunit of the insulin receptor. Incubation of synaptosomes with insulin caused a dose-dependent inhibition of specific sodium-sensitive [3H]norepinephrine uptake. Insulin inhibition of [3H]norepinephrine uptake was mediated by a decrease in active uptake sites without any effects in the Km, and was specific for insulin since related and unrelated peptides influenced the uptake in proportion to their structural similarity with insulin. These observations indicate that synaptosomes prepared from the adult rat brain possess specific insulin receptors and insulin has inhibitory effects on norepinephrine uptake in the preparation.

Original languageEnglish
Pages (from-to)297-303
Number of pages7
JournalNeurochemical Research
Volume13
Issue number4
DOIs
StatePublished - Apr 1988
Externally publishedYes

Keywords

  • Insulin Receptors
  • brain
  • neuronal cells
  • norepinephrine

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