Saltiel A R, Osterman D G, Darnell J C, Sorbara-Cazan L R, Chan B L, Low M G, Cuatrecasas P
Laboratory of Biochemical Endocrinology, Rockefeller University, New York 10021.
Philos Trans R Soc Lond B Biol Sci. 1988 Jul 26;320(1199):345-58. doi: 10.1098/rstb.1988.0081.
The molecular events involved in the cellular actions of insulin remain unexplained. Some of the acute actions of the hormone may be due to the intracellular generation of a chemical substance which modulates certain enzyme activities. Such an enzyme-modulating substance has been identified as an inositol phosphate-glycan, produced by the insulin-sensitive hydrolysis of a glycosyl-phosphatidylinositol (glycosyl-PtdIns) precursor. This precursor glycolipid is structurally similar to the glycosyl-phosphoinositide membrane protein anchor. The exposure of fat, liver or muscle cells to insulin results in the hydrolysis of glycosyl-PtdIns, giving rise to the inositol phosphate glycan and diacylglycerol. This hydrolysis reaction is catalysed by a glycosyl-PtdIns-specific phospholipase C. This enzyme has been characterized and purified from a plasma membrane fraction of liver. This reaction also results in the acute release of certain glycosyl-PtdIns-anchored proteins from the cell surface. Elucidation of the functional role of glycosyl-phosphoinositides in the generation of second messengers or the release of proteins may provide further insights into the pleiotropic nature of insulin action.
胰岛素细胞作用所涉及的分子事件仍未得到解释。该激素的一些急性作用可能归因于一种调节某些酶活性的化学物质在细胞内的生成。这种酶调节物质已被鉴定为一种肌醇磷酸聚糖，它由糖基磷脂酰肌醇（糖基-PtdIns）前体经胰岛素敏感水解产生。这种前体糖脂在结构上与糖基磷酸肌醇膜蛋白锚定物相似。脂肪、肝脏或肌肉细胞暴露于胰岛素会导致糖基-PtdIns水解，产生肌醇磷酸聚糖和二酰基甘油。这种水解反应由一种糖基-PtdIns特异性磷脂酶C催化。该酶已从肝脏的质膜部分得到表征和纯化。此反应还会导致某些糖基-PtdIns锚定蛋白从细胞表面急性释放。阐明糖基磷酸肌醇在第二信使生成或蛋白质释放中的功能作用，可能会为胰岛素作用的多效性本质提供进一步的见解。
