Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of cAMP phosphodiesterase.
Insulin-stimulated hydrolysis of a novel glycolipid generates modulators of cAMP phosphodiesterase.
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胰岛素刺激的新型糖脂水解产生 cAMP 磷酸二酯酶调节剂。
DOI：
10.1126/science.3016898
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Cuatrecasas,P
中科院分区：
文献类型：
--
作者：
Saltiel,AR;Fox,JA;Sherline,P;Cuatrecasas,P
胰岛素作用可能涉及细胞内产生调节某些关键酶的低分子量物质。通过掺入放射性标记的前体，在培养的心肌细胞中评价了调节腺苷3′，5 ′-单磷酸二酯酶活性的两种物质的产生。胰岛素引起一种化学性质不确定的膜糖脂的快速水解，导致两种相关的复合碳水化合物和甘油二酯的产生。糖脂前体和水性产物均通过用放射性肌醇和葡糖胺标记来监测。耗尽标记的前体和标记的水溶性产物和甘油二酯的外观发生在激素处理后30秒内，然后快速再合成的前体。放射性标记的水性产物在色谱和色谱上与来自相同细胞的胰岛素产生的磷酸二酯酶调节活性相同。纯化的放射性标记物质和生物活性物质具有相似的化学性质。糖脂前体的水解和随后生成的产物可以通过将提取的脂质与磷脂酰肌醇特异性磷脂酶C孵育来再现。这些研究表明，胰岛素刺激内源性、选择性磷脂酶C活性，该活性水解新型糖脂，导致产生含有肌醇和葡糖胺的复合碳水化合物-磷酸盐物质，该物质可能介导激素的某些作用。
Insulin action may involve the intracellular generation of low molecular weight substances that modulate certain key enzymes. The production of two substances that regulate the activity of adenosine 3′,5′-monophosphate phosphodiesterase was evaluated in cultured myocytes by incorporation of radiolabeled precursors. Insulin caused the rapid hydrolysis of a chemically undefined membrane glycolipid, resulting in the production of two related complex carbohydrates as well as diacylglycerol. Both the glycolipid precursor and the aqueous products were monitored by labeling with radioactive inositol and glucosamine. Depletion of the labeled precursor and the appearance of labeled water-soluble products and diacylglycerol occurred within 30 seconds after hormone treatment and was followed by rapid resynthesis of the precursor. The aqueous products that were radioactively labeled appeared chromatographically and electrophoretically identical to phosphodiesterase modulating activities produced by insulin from the same cells. The purified radiolabeled and bioactive substances had similar chemical properties. Hydrolysis of the glycolipid precursor and subsequent generation of products could be reproduced by incubation of extracted lipids with a phosphatidylinositol-specific phospholipase C. These studies suggest that insulin stimulates an endogenous, selective phospholipase C activity that hydrolyzes a novel glycolipid, resulting in the generation of a complex carbohydrate-phosphate substance containing inositol and glucosamine that may mediate some of the actions of the hormone.