Blachier F, Malaisse W J
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Biochim Biophys Acta. 1988 Jun 30;970(2):222-9. doi: 10.1016/0167-4889(88)90182-6.
Endogenous ATP is thought to play a key regulatory role in nutrient-stimulated insulin release. The present study deals with the effect of exogenous ATP and its stable analog alpha, beta-methylene ATP upon pancreatic islet function. Both alpha, beta-methylene ATP (5.0 microM to 0.2 mM) and ATP (0.3-3.0 mM) caused a rapid and concentration-related increase in insulin output by rat islets incubated or perfused at an intermediate concentration of D-glucose (8.3 mM). The effect of the ATP analog faded out at both lower and higher D-glucose concentrations. In the presence of 8.3 mM D-glucose, ATP also increased both 86Rb and 45Ca outflow from prelabelled islets. The cationic response to ATP persisted in the absence of extracellular Ca2+ and, hence, was reminiscent of that evoked by cholinergic agents. Like carbamylcholine, ATP caused a dose-related increase in the production of [3H]inositol phosphates from prelabelled islets or tumoral islet cells (RINm5F line). The latter effect was duplicated by alpha, beta-methylene ATP and unaffected by atropine. It is speculated that ATP, liberated together with insulin at the exocytotic site, might participate in a positive feedback control of insulin release.
内源性三磷酸腺苷（ATP）被认为在营养物质刺激的胰岛素释放过程中发挥关键的调节作用。本研究探讨外源性ATP及其稳定类似物α，β-亚甲基ATP对胰岛功能的影响。α，β-亚甲基ATP（5.0微摩尔至0.2毫摩尔）和ATP（0.3 - 3.0毫摩尔）均使在中等浓度D-葡萄糖（8.3毫摩尔）下孵育或灌注的大鼠胰岛的胰岛素分泌迅速且呈浓度依赖性增加。ATP类似物的作用在较低和较高D-葡萄糖浓度下均消失。在8.3毫摩尔D-葡萄糖存在的情况下，ATP还增加了预先标记的胰岛中86Rb和45Ca的流出。在没有细胞外Ca2 +的情况下，对ATP的阳离子反应仍然存在，因此，这让人联想到胆碱能药物引起的反应。与氨甲酰胆碱一样，ATP使预先标记的胰岛或肿瘤胰岛细胞（RINm5F系）中[3H]肌醇磷酸的生成呈剂量依赖性增加。后一种作用可被α，β-亚甲基ATP复制，且不受阿托品影响。据推测，在胞吐部位与胰岛素一起释放的ATP可能参与胰岛素释放的正反馈控制。
