Article

Insulin receptors in the brain: structural and physiological characterization. Neurochem Res 13: 297-303

Department of Physiology, University of Florida College of Medicine, Gainesville 32610.
Neurochemical Research (Impact Factor: 2.55). 05/1988; 13(4):297-303. DOI: 10.1007/BF00972477
Source: PubMed

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.

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    • "IGF-I itself has been detected in astrocytes and neurons of the central nervous system (CNS) (Garcia-Segura et al. 1991; Garcia-Estrada et al. 1992). The receptors for insulin (IR) and IGF-I (IGFIR) as well as other components of these signaling pathways are expressed throughout the mammalian brain with particularly high concentrations in the hypothalamus, the hippocampus, and the cerebral cortex (Raizada et al. 1988; Unger et al. 1989; Pons 1991 #392). "
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    • "However, initial studies of insulin's regulation of the norepinephrine transporter (NET) function were more consistent. For example, insulin inhibits NE uptake in whole brain neuronal cultures, dissociated brain cells, and whole brain synaptosomes (Boyd et al., 1985, 1986; Masters et al., 1987; Raizada et al., 1988). Furthermore, Figlewicz et al. demonstrated that nanomolar concentrations of acute insulin decrease NE uptake from both hypothalamic and hippocampal rat slices (Figlewicz et al., 1993), and that insulin also inhibits NE uptake in PC12 cells which endogenously synthesize NE and express NET (Figlewicz et al., 1993). "
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    • "Importantly, previous studies implicate a clear role for insulin, a metabolic hormone, in the regulation of NET function. Indeed, insulin inhibits NE uptake in whole brain neuronal cultures, dissociated brain cells, and whole brain synaptosomes (Boyd et al., 1985; Boyd et al., 1986; Masters et al., 1987; Raizada et al., 1988). Furthermore, Figlewicz et al. demonstrated the ability of nanomolar concentrations of acute insulin to decrease NE uptake from both hypothalamic and hippocampal slices (Figlewicz et al., 1993). "
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