Insulin and phorbol ester stimulate conductive Na+ transport through a common pathway.
Insulin and phorbol ester stimulate conductive Na+ transport through a common pathway.
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胰岛素和佛波酯通过共同途径刺激传导性钠转运。
DOI：
10.1073/pnas.85.3.963
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发表时间：
1988
影响因子：
11.1
通讯作者：
O'Brien,TG
中科院分区：
文献类型：
--
作者：
Civan,MM;Peterson-Yantorno,K;O'Brien,TG
胰岛素刺激钠离子跨蛙皮肤、蟾蜍膀胱和远端肾单位的转运。这种刺激反映了顶膜Na+通透性的增加和对基底膜Na，K交换泵的刺激。相当多的间接证据表明，胰岛素的顶端排钠作用是通过激活蛋白激酶C来实现的。然而，目前还没有直接的信息来证明胰岛素和蛋白激酶C在刺激皮肤Na+转运方面确实有共同的途径。在目前的工作中，我们研究了胰岛素与佛波酯(PMA)的相互作用，佛波酯是一种已知的蛋白激酶C激活剂。用另一种蛋白激酶C激活剂1，2-二辛酰甘油预先孵育皮肤，增加了基线Na+转运，并降低了随后对PMA的钠反应。与PMA预先孵育可显著降低胰岛素随后的升钠作用。这种效应似乎并不主要反映PMA诱导的胰岛素受体内在化。胰岛素受体定位于蛙皮肤的基底外侧表面，但在这一表面应用PMA在降低对胰岛素的反应方面远不如粘膜治疗有效。与D-鞘氨醇(一种蛋白激酶C的抑制剂)预先孵育，也会减少胰岛素的促钠作用。目前的结果表明，胰岛素和蛋白激酶C在刺激钠离子跨蛙皮肤运输方面具有共同的途径。这些数据与这样一个概念是一致的，即胰岛素对青蛙皮肤的纳盐作用至少部分是通过激活蛋白激酶C来调节的。
Insulin stimulates Na+ transport across frog skin, toad urinary bladder, and the distal renal nephron. This stimulation reflects an increase in apical membrane Na+ permeability and a stimulation of the basolateral membrane Na,K-exchange pump. Considerable indirect evidence has suggested that the apical natriferic effect of insulin is mediated by activation of protein kinase C. However, no direct information has been available documenting that insulin and protein kinase C indeed share a common pathway in stimulating Na+ transport across frog skin. In the present work, we have studied the interaction of insulin and phorbol 12-myristate 13-acetate (PMA), a documented activator of protein kinase C. Preincubation of skins with 1,2-dioctanoylglycerol, another activator of protein kinase C, increases baseline Na+ transport and reduces the subsequent natriferic response to PMA. Preincubation with PMA markedly reduces the subsequent natriferic action of insulin. This effect does not appear to primarily reflect PMA-induced internalization of insulin receptors. The insulin receptors are localized on the basolateral surface of frog skin, but the application of PMA to this surface is much less effective than mucosal treatment in reducing the response to insulin. Preincubation with D-sphingosine, an inhibitor of protein kinase C, also reduces the natriferic action of insulin. The current results provide documentation that insulin and protein kinase C share a common pathway in stimulating Na+ transport across frog skin. The data are consistent with the concept that the natriferic effect of insulin on frog skin is, at least in part, mediated by activation of protein kinase C.