Weaver D C, McDaniel M L, Naber S P, Barry C D, Lacy P E
Diabetes. 1978 Dec;27(12):1205-14. doi: 10.2337/diab.27.12.1205.
The rate of alloxan-induced insulin release was measured from rat islets maintained in a simple perifusion system. Insulin release during the five-minute exposure to alloxan reached its maximum rate after two to three minutes of the exposure and then rapidly declined. This insulin release was dependent upon extracellular calcium and was associated with an increased 45Ca uptake by isolated islets. Once exposed to alloxan, however, the islets did not release insulin when stimulated again with D-glucose or alloxan. These effects of alloxan on insulin release (stimulation and subsequent inhibition) and the increased 45Ca uptake were prevented by the presence of 3-0-methyl-D-glucose during the alloxan exposure. These findings indicate a close correlation between alloxan-induced insulin release and the subsequent inhibition of further insulin release. D-glucose, when present during the entire five-minute exposure to alloxan, protected competitively against alloxan inhibition of insulin release. In addition, D-glucose, when present immediately after brief (one to three minutes) alloxan exposures, reversed some of the subsequent inhibition of insulin release. These findings suggest that alloxan and D-glucose were competing for a common site on the beta-cell. The possibility of this site being a receptor responsible for the initiation of insulin release is discussed.
在一个简单的灌流系统中，测定了四氧嘧啶诱导的大鼠胰岛胰岛素释放速率。在暴露于四氧嘧啶的五分钟内，胰岛素释放在暴露两到三分钟后达到最大速率，然后迅速下降。这种胰岛素释放依赖于细胞外钙，并与分离的胰岛对45Ca摄取增加有关。然而，一旦暴露于四氧嘧啶，当再次用D-葡萄糖或四氧嘧啶刺激时，胰岛不再释放胰岛素。在四氧嘧啶暴露期间存在3-0-甲基-D-葡萄糖可防止四氧嘧啶对胰岛素释放的这些影响（刺激和随后的抑制）以及45Ca摄取增加。这些发现表明四氧嘧啶诱导的胰岛素释放与随后对进一步胰岛素释放的抑制之间存在密切相关性。在整个暴露于四氧嘧啶的五分钟内存在D-葡萄糖时，可竞争性地保护胰岛免受四氧嘧啶对胰岛素释放的抑制。此外，在短暂（一到三分钟）暴露于四氧嘧啶后立即存在D-葡萄糖时，可逆转部分随后对胰岛素释放的抑制。这些发现表明四氧嘧啶和D-葡萄糖在β细胞上竞争一个共同位点。讨论了该位点作为负责启动胰岛素释放的受体的可能性。
