Autoradiographic localization of insulin receptors in rat brain: Prominence in olfactory and limbic areas

Hill, Joanna M.; Lesniak, Maxine A.; Pert, Candace B.; Roth, Jesse

doi:10.1016/0306-4522(86)90082-5

Cited by 387 publications

(193 citation statements)

References 26 publications

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“…Interestingly, the distribution of the insulin receptor has been reported to correspond with the distribution of neuropeptides (36). We were able to show in previous colocalization studies that insulin receptors are present on vasopressin-containing neurons in the supraoptic nucleus and on somatostatin-containing neurons in the periventricular nucleus (20).…”

Section: Discussionsupporting

confidence: 51%

Location of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor.

Moss

Unger

Moxley

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Cellular regulation by certain growth factor receptors and protooncogene products involves tyrosine kinase activity with the resultant tyrosine phosphorylation of protein substrates. In the present report we describe the distribution of phosphotyrosine-containing material detected by immunoytochemistry (ICC) in the rat forebrain. Specificity of the affinity-purified antibody against phosphotyrosine used in the ICC technique was demonstrated by the ability of phosphotyrosine and p-nitrophenyl phosphate but not phosphoserine, phosphothreonine, or L-tyrosine to inhibit the immunostaining reaction. With ICC, relatively high amounts of phosphotyrosine-positive material were observed in neurons in specific structures that included the supraoptic, paraventricular, and arcuate nuclei; the median eminence; medial habenula; subfornical organ; and piriform cortex. Moderate to high amounts were present in the cerebral cortical layers II-IV and in the pyramidal cell layer of the hippocampus. Small to moderate amounts were detected in a few other locations. Glial elements showed minimal staining. Other areas of the rat forebrain failed to react with this antibody. Importantly, the distribution of the areas positive for phosphotyrosine agreed to a remarkable extent with the distribution of the brain insulin receptor, which itself has tyrosine kinase activity. These findings suggest a relationship between the insulin receptor and the increased phosphotyrosine content of these neurons and support the concept that the brain insulin receptor is active in vivo.A number of growth factor receptors and protein products of retroviral oncogenes and protooncogenes are proteintyrosine kinases (1). This enzymatic activity apparently plays an important role in the mediation of the actions of these regulatory proteins (1,2). Although much of the work on tyrosine kinases has focused on growth regulation, recent findings in the nonproliferating cells of the central nervous system demonstrate the presence of relatively large amounts of tyrosine kinase activity (2, 3). For example, the c-src gene product, pp6O src, is widely distributed in the adult rat brain (4) and is expressed throughout brain development (5)(6)(7)(8).Receptors for insulin and insulin-like growth factor 1 (IGF-1) are also present in specific brain regions (9)(10)(11)(12)(13)). Both receptors demonstrate ligand-controlled autophosphorylation on specific tyrosines and tyrosine phosphorylation of endogenous proteins (14-17), although the distribution of the two receptor types differs in the rat brain (12,13,18).Little information is available on the in vivo activation of these kinases in the central nervous system. Previous work has used brain tissue extracts to examine tyrosine kinase activity (19), an approach that does not provide direct evidence of in vivo tyrosine kinase activity nor does it establish the precise location of areas rich in tyrosine phosphorylation.In the present investigation, we have examined the rat forebrain with an immunocytochemical technique (I...

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Section: Discussionsupporting

confidence: 51%

Location of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor.

Moss

Unger

Moxley

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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“…This is interesting since decreased numbers of dopamine receptors or dopamine concentrations have a role in obesity (Wang et al, 2001), a condition that is frequently associated with type 2 diabetes. The brain is rich in insulin receptors (Bruning et al, 2000;Hill et al, 1986;Das, 2001e). Insulin receptor tyrosine kinase substrate p58=53 and the insulin receptor are components of synapses in the CNS (Abott et al, 1999).…”

Section: Ventromedial Hypothalamic Lesion and Type 2 Diabetes Mellitusmentioning

confidence: 99%

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent diabetes mellitus?

Das¹

2003

Eur J Clin Nutr

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It is suggested that the negative correlation between breast-feeding and insulin resistance and diabetes mellitus can be related to the presence of significant amounts of long-chain polyunsaturated fatty acids in the human breast milk. Based on this, it is proposed that provision of adequate amounts of long chain polyunsaturated fatty acids during the critical periods of brain growth and development can prevent or postpone the development diabetes mellitus.

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“…What is their impact on insulin and IGF-I function? It should be noted that the distribution of insulin receptors in the brain largely overlaps with that of the IGF-I receptor (Hill et al, 1986), although the latter has a much broader distribution. This supports the possibility that the same brain cells expressing insulin receptors also coexpress IGF-I receptors, which means that at least in theory, the possibility of forming hybrid receptors exists.…”

Section: Igf-i and Insulin Signaling: Role Of Igf-i And Insulin Homo mentioning

confidence: 99%

Toward a comprehensive neurobiology of IGF‐I

Torres‐Alemán

2010

Developmental Neurobiology

152

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Imatinib is the drug of first choice for most patients with chronic phase chronic myeloid leukemia (CML). Although it is generally well tolerated, a number of hematological and nonhematological side‐effects have been described. We report here that imatinib induces hypophosphatemia in a high proportion of our series of CML patients previously treated with interferon α, and that this previously unreported side effect is associated with response. Am. J. Hematol., 2007. © 2006 Wiley‐Liss, Inc.

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Autoradiographic localization of insulin receptors in rat brain: Prominence in olfactory and limbic areas

Cited by 387 publications

References 26 publications

Location of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor.

Location of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor.

Can perinatal supplementation of long-chain polyunsaturated fatty acids prevent diabetes mellitus?

Toward a comprehensive neurobiology of IGF‐I

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