IMMUNOCYTOCHEMICAL DETECTION OF INSULIN-RECEPTOR SUBSTRATE-1 (IRS-1) IN RAT-BRAIN - COLOCALIZATION WITH PHOSPHOTYROSINE
IMMUNOCYTOCHEMICAL DETECTION OF INSULIN-RECEPTOR SUBSTRATE-1 (IRS-1) IN RAT-BRAIN - COLOCALIZATION WITH PHOSPHOTYROSINE
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DOI：
10.1016/0167-0115(93)90355-c
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发表时间：
1993-10-20
影响因子：
--
通讯作者：
WHITE, MF
中科院分区：
文献类型：
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作者：
BASKIN, DG;SIPOLS, AJ;WHITE, MF
在外周胰岛素敏感组织中，胰岛素受体底物(IRS-1)在细胞受到胰岛素或胰岛素样生长因子-1(IGF-1)刺激后立即进行酪氨酸磷酸化，可能是胰岛素/IGF-1受体酪氨酸激酶与调节细胞生长和代谢的酶之间的分子纽带。与胰岛素/IGF-1在大脑中的作用有关的一个基本问题是，IRS-1是否由神经元表达。本研究用免疫细胞化学方法，用多克隆IRS-1抗血清对脑内含IRS-1免疫反应的细胞进行了定位，并与用多克隆磷酸酪氨酸抗血清对磷酸酪氨酸的免疫染色进行了比较。ABC-过氧化物酶免疫组织化学染色和冰冻切片结果表明，IRS-1免疫反应阳性物质存在于大鼠前脑的许多神经元胞体中，尤其是缰核、大脑皮质和梨状皮质。在下丘脑，IRS-1免疫反应阳性神经元见于室旁核、视上核和弓状核。脉络丛IRS-1染色较深。对IRS-1染色的细胞群体也显示出很强的磷酸酪氨酸免疫染色。需要在细胞水平上进行研究，以证实IRS-1和胰岛素或IGF-1受体在相同的神经元以及脉络丛细胞中的共同表达。这一结果首次证实了成年哺乳动物脑内神经元表达IRS-1。这些发现与假设一致，即大脑中的胰岛素和IGF-I的作用涉及与周围组织相同的信号转导机制。
In peripheral insulin-sensitive tissues, insulin receptor substrate (IRS-1) undergoes tyrosine phosphorylation immediately after cells are stimulated by insulin or insulin-like growth factor-I (IGF-1), and may function as a molecular link between insulin/IGF-1 receptor tyrosine kinases and enzymes regulating cell growth and metabolism. A fundamental question pertaining to insulin/IGF-1 action in the brain is whether IRS-1 is expressed by neurons. In this study, the distribution of cells containing immunoreactivity to IRS-1 in the brain was determined by immunocytochemistry with polyclonal IRS-1 antiserum, and compared to the localization of immunostaining for phosphotyrosine using polyclonal phosphotyrosine antiserum. The immunostaining results with ABC-peroxidase method and cryostat sections showed the presence of IRS-1 immunoreactivity in many neuron cell bodies throughout the rat forebrain, particularly in the habenula, cerebral cortex and piriform cortex. In the hypothalamus, IRS-1 immunostaining was present in neurons of the paraventricular nucleus, supraoptic nucleus, and arcuate nucleus. The choroid plexus stained intensely for IRS-1. The populations of cells that stained for IRS-1 also showed strong immunostaining for phosphotyrosine. Studies at the cellular level are needed to verify coexpression of IRS-1 and receptors for insulin or IGF-1 by the same neurons, as well as in cells of the choroid plexus. The present results are the first demonstration of IRS-1 expression by neurons in adult mammalian brain. These findings are consistent with the hypothesis that insulin and IGF-I actions in the brain involve signal transduction mechanisms common to those found in peripheral tissues.