Verspohl E J, Kaiser P, Wahl M, Ammon H P
Department of Pharmacology, University of Tübingen, West Germany.
Life Sci. 1988;43(3):209-19. doi: 10.1016/0024-3205(88)90310-4.
In isolated rat pancreatic islets maintained at a physiologic glucose concentration (5.6 mM) the effect of glucose on parameters which are known to be involved in the insulin secretion coupling such as NADPH, reduced glutathione (GSH), 86Rb+ efflux, and 45Ca++ net uptake were investigated. The insulinotropic effect of 16.7 mM glucose was decreased with the period of culturing during the first 14 days being significant after 2 days though in control experiments both protein content and ATP levels per islet were not affected and insulin content was only slightly decreased. Both NADPH and GSH decreased with time of culture. 86Rb+ efflux which is decreased by enhancing the glucose concentration from 3 to 5.6 mM in freshly isolated islets was not affected by culturing whatsoever, even not after 14 days of culture when there was no longer any insulin responsiveness to glucose. The 45Ca++ net uptake was decreased during culturing. The data indicate (1) that the diminished glucose-stimulated release of insulin during culturing is not due to cell loss or simple energy disturbances, (2) that more likely it is the result of a diminished 45Ca++ net uptake as a consequence of the inability of islet cells to maintain proper NADPH and GSH levels, and (3) that potassium (86Rb+) efflux may not be related to changes of NADPH and GSH.
在维持于生理葡萄糖浓度（5.6 mM）的离体大鼠胰岛中，研究了葡萄糖对已知参与胰岛素分泌偶联的参数的影响，如还原型辅酶Ⅱ（NADPH）、还原型谷胱甘肽（GSH）、86Rb⁺外流以及45Ca²⁺净摄取。在培养的前14天，16.7 mM葡萄糖的促胰岛素分泌作用随培养时间而降低，2天后这种降低很显著，不过在对照实验中，每个胰岛的蛋白质含量和ATP水平均未受影响，胰岛素含量仅略有下降。NADPH和GSH均随培养时间而降低。在新鲜分离的胰岛中，将葡萄糖浓度从3 mM提高到5.6 mM可降低86Rb⁺外流，而培养对其没有任何影响，即使在培养14天后，此时对葡萄糖已不再有胰岛素反应。培养期间45Ca²⁺净摄取减少。这些数据表明：（1）培养期间葡萄糖刺激的胰岛素释放减少并非由于细胞丢失或单纯的能量紊乱；（2）更有可能是胰岛细胞无法维持适当的NADPH和GSH水平导致45Ca²⁺净摄取减少的结果；（3）钾（86Rb⁺）外流可能与NADPH和GSH的变化无关。
