Welsh M
Diabetologia. 1982 Jul;23(1):54-60. doi: 10.1007/BF00257732.
Cultured mouse pancreatic islets were prelabelled with 2-3H-adenosine in order to monitor the efflux pattern of radioactivity and insulin. The outflow of radioactivity decreased continuously when the islets were perifused with glucose (1.67 mmol/l). When raising the glucose concentration to 16.7 mmol/l, there was a prompt inhibition of the radioactive efflux concomitant with an increased rate of insulin release. These effects were reversed when the high glucose challenge was withdrawn. Similar radioactive efflux patterns were obtained after addition of alpha-ketoisocaproic acid, leucine or pyruvate to the perifusion medium, and also when the islets were challenged with high glucose concentrations in the absence of calcium. Both antimycin A and glipizide stimulated the efflux of radioactivity, although only the addition of glipizide was accompanied by a stimulation of the insulin release. Nucleotides constituted approximately 90% of the total effluent radioactivity. Decrease in the radioactive AMP and ADP efflux due to high glucose was furthermore found to be the cause of the observed inhibition of the total radioactive efflux. The changes in radioactive efflux induced by glucose probably reflect changes in the intracellular concentrations of AMP and ADP. It is concluded that no simple correlation exists between radioactive efflux and insulin release and that changes in the intracellular concentrations of nucleotides may be an early event in the stimulus-secretion coupling of glucose-induced insulin release.
培养的小鼠胰岛用2-³H-腺苷进行预标记，以监测放射性和胰岛素的流出模式。当胰岛用葡萄糖（1.67 mmol/L）进行灌流时，放射性流出持续减少。当将葡萄糖浓度提高到16.7 mmol/L时，放射性流出迅速受到抑制，同时胰岛素释放速率增加。当撤除高糖刺激时，这些效应会逆转。在灌流培养基中添加α-酮异己酸、亮氨酸或丙酮酸后，以及在无钙情况下用高糖浓度刺激胰岛时，也获得了类似的放射性流出模式。抗霉素A和格列吡嗪均刺激放射性流出，尽管只有添加格列吡嗪时伴随着胰岛素释放的刺激。核苷酸约占流出总放射性的90%。此外，发现高糖导致的放射性AMP和ADP流出减少是观察到的总放射性流出抑制的原因。葡萄糖诱导的放射性流出变化可能反映了细胞内AMP和ADP浓度的变化。得出的结论是，放射性流出与胰岛素释放之间不存在简单的相关性，并且核苷酸细胞内浓度的变化可能是葡萄糖诱导的胰岛素释放刺激-分泌偶联中的早期事件。
