Kinetic and quantitative relationships between insulin release and 65Zn efflux from perifused islets.
Kinetic and quantitative relationships between insulin release and 65Zn efflux from perifused islets.
复制标题
胰岛素释放和 65Zn 从灌注胰岛流出之间的动力学和定量关系。
作者：
G. Grodsky;F. Schmid
锌释放和胰岛素分泌的动力学进行了比较，在灌流胰岛预先加载24小时与65锌。在没有可检测的胰岛素分泌的情况下，分数基础65锌释放是恒定的在3-5%/小时，在整个实验期间，这表明，基础流出的锌主要是从一个单一的颗粒外室。单独的葡萄糖（25 mM）引起65 Zn和胰岛素的迅速释放。先前使用细胞分级的研究表明，大约三分之一的胰岛65锌是在颗粒部分。因此，如果锌流出仅代表从颗粒共分泌的锌，则预期65 Zn与胰岛素的分泌比例约为0.33。然而，65锌胰岛素分泌分数的比例仅为0.16，表明葡萄糖不仅导致与储存的胰岛素相关的锌的共分泌，而且还独立地减少65锌从颗粒外来源的流出。在低葡萄糖浓度下，3-异丁基-1-甲基黄嘌呤（IBMX; 1 mM）不影响胰岛素或65 Zn外排;然而，葡萄糖加IBMX的组合导致65 Zn和胰岛素以约0.33的比率大量平行双相释放。用葡萄糖加毛喉素得到类似的结果。亮氨酸（20 mM）加IBMX引起胰岛素的特征性快速分泌，随时间推移而减弱。流出的65锌也迅速，然而，分泌的65锌胰岛素的比例逐渐增加，从一个接近理论值的共分泌在最初的峰值刺激结束时的0.70。即使在终止亮氨酸加IBMX刺激后，65 Zn流出仍持续。α-酮异己酸引起胰岛素分泌的类似刺激和减弱，但具有约0.33的一致的65 Zn与胰岛素分泌分数比。与亮氨酸和α-酮异己酸，刺激后65锌流出仍然升高。灌流未标记的锌（1 mM;抑制胰岛素分泌的浓度）引起迅速和持续释放的65锌;流出保持高至少30分钟后终止锌管理。结果扩大了以前的批次胰岛实验表明，锌和胰岛素可以暂时cosecreted在定量上与他们的存储比例一致的比例在颗粒中没有保存或细胞内再利用。此外，有65锌流出的非颗粒隔室的刺激或抑制，这取决于促分泌素。（400字处截断摘要）
The kinetics of zinc release and insulin secretion were compared in perifused islets previously loaded for 24 h with 65Zn. In the absence of detectable insulin secretion, fractional basal 65Zn release was constant at 3-5%/h throughout the experimental periods, suggesting that basal efflux of zinc is primarily from a single extragranular compartment. Glucose (25 mM) alone caused a prompt release of both 65Zn and insulin. Previous studies using cell fractionation showed that approximately one third of islet 65Zn is in the granular fraction. Thus, if zinc efflux represents only that being cosecreted from the granule, a 65Zn to insulin fractional secretion ratio of approximately 0.33 would be expected. However, the ratio of 65Zn to insulin fractional secretion was only 0.16, indicating that glucose not only causes cosecretion of zinc associated with stored insulin, but also independently decreases 65Zn efflux from extragranular sources. At low glucose concentrations, 3-isobutyl-1-methylxanthine (IBMX; 1 mM) did not affect either insulin or 65Zn efflux; however, the combination of glucose plus IBMX caused a large and parallel biphasic release of both 65Zn and insulin at ratios approximating 0.33. Similar results were obtained with glucose plus forskolin. Leucine (20 mM) plus IBMX caused a characteristic rapid secretion of insulin which waned with time. Efflux of 65Zn was also prompt; however, the ratio of secreted 65Zn to insulin gradually increased during stimulation from a near-theoretical value for cosecretion at the initial peak to 0.70 by the end of the stimulation. 65Zn efflux was sustained even after termination of the leucine plus IBMX stimulus. alpha-Ketoisocaproic acid caused a similar stimulation and waning of insulin secretion, but with a consistent 65Zn to insulin fractional secretion ratio of about 0.33. With both leucine and alpha-ketoisocaproic acid, poststimulatory 65Zn efflux remained elevated. Perifusion of unlabeled zinc (1 mM; a concentration that inhibits insulin secretion) caused prompt and sustained release of 65Zn; efflux remained high at least 30 min after termination of zinc administration. Results expand previous batch islet experiments to show that zinc and insulin can be temporally cosecreted at ratios quantitatively consistent with their storage ratio in the granules without conservation or intracellular reutilization. In addition, there is 65Zn efflux from nongranular compartments which is stimulated or inhibited, depending on the secretagogue.(ABSTRACT TRUNCATED AT 400 WORDS)