Clements R S, Rhoten W B
J Clin Invest. 1976 Mar;57(3):684-91. doi: 10.1172/JCI108325.
Since many cell types have been shown to respond to extracellular stimulation with a rapid increase in phosphatidylinositol turnover, the present studies were undertaken to determine whether carbohydrate-stimulated insulin secretion from the isolated rat pancreatic islet is accompanied by detectable alterations in the phosphatidylinositol metabolism of this tissue. We have demonstrated that rat pancreatic islets incubated with tritiated myo-inositol rapidly incorporate radioactivity into islet phosphatidylinositol. Incubation of prelabeled islets with elevated concentrations of carbohydrates which stimulate insulin secretion (D-glucose and D-mannose) results in a decrease in the recovery of lipid-bound radioactivity, whereas incubation with carbohydrates which do not stimulate insulin secretion (D-galactose and myo-inositol) has no effect upon the recovery of lipid-bound radioactivity. Within 2 min of exposure of prelabeled islets to elevated concentrations of D-glucose, a decrease in the recovery of [2-3H]myo-inositol-derived radioactivity in islet phosphatidylinositol can be demonstrated. When islets prelabeled with [2-3H]myo-inositol are perifused with elevated concentrations of D-glucose or D-mannose (but not D-galactose or myoinositol) a rapid and transient increase in the rate of extracellular release of water-soluble radioactivity is observed. Since a significant fraction of the radioactivity released under these conditions is in the form of myo-inositol phosphate, cyclic myo-inositol-1,2-phosphate, and glycerophosphorylmyo-inositol, it is presumably derived from the cleavage of labeled islet phosphatidylinositol. It is speculated that alterations in the metabolism of myo-inositol-containing phospholipids may have a functional role in the process of insulin secretion from the pancreatic beta cell.
由于许多细胞类型已被证明会对细胞外刺激做出反应，导致磷脂酰肌醇周转率迅速增加，因此进行了本研究，以确定从分离的大鼠胰岛中碳水化合物刺激的胰岛素分泌是否伴随着该组织磷脂酰肌醇代谢的可检测变化。我们已经证明，用氚标记的肌醇孵育的大鼠胰岛会迅速将放射性掺入胰岛磷脂酰肌醇中。用刺激胰岛素分泌的高浓度碳水化合物（D-葡萄糖和D-甘露糖）孵育预先标记的胰岛会导致脂质结合放射性的回收率降低，而用不刺激胰岛素分泌的碳水化合物（D-半乳糖和肌醇）孵育对脂质结合放射性的回收率没有影响。在预先标记的胰岛暴露于高浓度D-葡萄糖的2分钟内，可以证明胰岛磷脂酰肌醇中[2-3H]肌醇衍生放射性的回收率降低。当用[2-3H]肌醇预先标记的胰岛用高浓度的D-葡萄糖或D-甘露糖（但不是D-半乳糖或肌醇）进行灌流时，观察到水溶性放射性的细胞外释放速率迅速且短暂增加。由于在这些条件下释放的放射性的很大一部分是以肌醇磷酸、环肌醇-1,2-磷酸和甘油磷酸肌醇的形式存在，推测它可能来自标记的胰岛磷脂酰肌醇的裂解。据推测，含肌醇磷脂的代谢变化可能在胰腺β细胞胰岛素分泌过程中起功能性作用。
