Ortsäter H, Liss P, Lund P E, Akerman K E, Bergsten P
Department of Medical Cell Biology, Uppsala University, Sweden.
Diabetologia. 2000 Oct;43(10):1313-8. doi: 10.1007/s001250051528.
AIMS/HYPOTHESIS: The role of beta-cell metabolism for generation of oscillatory insulin release was investigated by simultaneous measurements of oxygen tension (pO2) and insulin release from individual islets of Langerhans.
Individual islets isolated from the ob/ob-mice were perifused. Insulin in the perifusate was measured with a sensitive ELISA and PO2 with a modified Clark-type electrode inserted into the islets.
In the presence of 3 mmol/l D-glucose, PO2 was 102 +/- 9 mmHg and oscillatory (0.26 +/- 0.04 oscillations/min). Corresponding insulin measurements showed oscillatory release with similar periodicity (0.25 +/- 0.02 oscillations/min). When the D-glucose concentration was increased to 11 mmol/l, PO2 decreased by 30% to 72 +/- 10 mmHg with maintained frequency of the oscillations. Corresponding insulin secretory rate rose from 5 +/- 2 to 131 +/- 16 pmol x g(-1) x s(-1) leaving the frequency of the insulin pulses unaffected. The magnitude of glucose-induced change in pO2 varied between islets but was positively correlated to the amount of insulin released (r2 = 0.85). When 1 mmol/l tolbutamide was added to the perifusion medium containing 11 mmol/l glucose no change in average oscillatory pO2 was observed despite a doubling in the secretory rate. When 8 mmol/l 3-oxymethyl glucose was added to perifusion medium containing 3 mmol/l D-glucose, neither pO2 nor insulin release of the islets were changed. Temporal analysis of oscillations in pO2 and insulin release revealed that maximum respiration correlated to maximum or close to maximum insulin release.
CONCLUSION/INTERPRETATION: The temporal relation between oscillations in pO2 and insulin release supports a role for metabolic oscillations in the generation of pulsatile insulin release.
目的/假设：通过同时测量朗格汉斯胰岛中氧张力（pO2）和胰岛素释放，研究β细胞代谢在产生振荡性胰岛素释放中的作用。
对从ob/ob小鼠分离出的单个胰岛进行灌流。用灵敏的酶联免疫吸附测定法（ELISA）测量灌流液中的胰岛素，并用插入胰岛的改良型Clark电极测量pO2。
在3 mmol/l D-葡萄糖存在下，pO2为102±9 mmHg，呈振荡性（0.26±0.04次振荡/分钟）。相应的胰岛素测量显示出具有相似周期的振荡性释放（0.25±0.02次振荡/分钟）。当D-葡萄糖浓度增加到11 mmol/l时，pO2下降30%至72±10 mmHg，振荡频率维持不变。相应的胰岛素分泌率从5±2上升至131±16 pmol×g(-1)×s(-1)，胰岛素脉冲频率未受影响。葡萄糖诱导的pO2变化幅度在不同胰岛间有所不同，但与胰岛素释放量呈正相关（r2 = 0.85）。当向含有11 mmol/l葡萄糖的灌流培养基中添加1 mmol/l甲苯磺丁脲时，尽管分泌率翻倍，但平均振荡pO2未观察到变化。当向含有3 mmol/l D-葡萄糖的灌流培养基中添加8 mmol/l 3-氧甲基葡萄糖时，胰岛的pO2和胰岛素释放均未改变。对pO2和胰岛素释放振荡的时间分析表明，最大呼吸与最大或接近最大胰岛素释放相关。
结论/解读：pO2振荡与胰岛素释放之间的时间关系支持代谢振荡在产生搏动性胰岛素释放中起作用。
