Insulin receptors in the brain: Structural and physiological characterization

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 of 125I-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 of 125I-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 beta 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.

Insulin in the Brain: Sources, Localization and Functions

“…On the other hand, insulin is found to be able to increase the turnover rate of epinephrine and norepinephrine [214]. The effects of insulin on norepinephrine have been investigated in dissociated brain cells and synaptosomes prepared from the adult rat brain, and it is shown that norepinephrine uptake is inhibited by insulin [215,216]. Similar results are also reported in cell culture studies [217,218].…”

Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach

“…IR mRNA is abundantly present in neuronal somata (Schwartz et al, 1992). The neuronal IR binds insulin in a highly specific and rapid manner (Raizada et al, 1988). It has been hypothesized that the differing distribution patterns of insulin-1 and IRs in the brain may suggest that IRs in different brain regions may use insulin from different sources, either peripherally or locally synthesized, for cell-to-cell communication and neuronal signal transduction (Zhao et al 2004).…”

Brain Insulin Receptors and Spatial Memory

“…Consistent with its enriched distribution in adrenergic terminals, insulin is found to promote central catecholaminergic activities by releasing both epinephrine and norepinephrine (20), inhibiting synaptic reuptake of norepinephrine (21), and altering catecholomine kinetics (22). In the hippocampus, insulin is reported to enhance ␣1 adrenergic receptor activity, leading to stimulation of membrane phosphoinositol turnover * The costs of publication of this article were defrayed in part by the payment of page charges.…”