Glucose-stimulated oscillations in free cytosolic ATP concentration imaged in single islet β-cells -: Evidence for a Ca2+-dependent mechanism
Glucose-stimulated oscillations in free cytosolic ATP concentration imaged in single islet β-cells -: Evidence for a Ca2+-dependent mechanism
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DOI：
10.2337/diabetes.51.2007.s162
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发表时间：
2002-02-01
期刊：
影响因子：
7.7
通讯作者：
Rutter, GA
中科院分区：
文献类型：
--
作者：
Ainscow, EK;Rutter, GA
正常的葡萄糖刺激的胰岛素分泌是脉动的，但这种脉动背后的分子机制还知之甚少。细胞内游离[ATP]/[ADP]比值的波动是一种可能的机制，因为它们可能会导致ATP敏感的K+通道活动的波动，从而导致振荡的钙内流。通过腺病毒载体在单个人或小鼠胰岛β细胞中表达的重组萤火虫荧光素酶成像后，我们在这里报告了胞内游离ATP浓度的振荡，并且这些振荡受到葡萄糖的影响。在人β细胞中，在3和15 mmoL/L的葡萄糖浓度下都观察到了振荡，但在较高的葡萄糖浓度下振荡的波长更长(167vs.66 S)。小鼠胰岛β细胞只有在葡萄糖浓度升高时才表现出胞内游离[Ca~(2+)]和[ATP]的振荡，两者的振荡周期均为12 0 S。为了探讨[Ca~(2+)]和[ATP]振荡之间的因果关系，我们在MIN6β细胞群体中进一步研究了两者的调节。在无钙条件下，葡萄糖浓度为3和30 mmol/L时，MIN6细胞胞浆[Ca~(2+)]降低，而[ATP]升高。清除外在的钙离子可增加[ATP]，这可能是通过减少内质网钙-ATPase对ATP的消耗而实现的。这些结果使得可以构建驱动营养诱导的胰岛素分泌的β细胞代谢振荡器的模型。糖尿病51(补充1)：5162-5170,2002。
Normal glucose-stimulated insulin secretion is pulsatile, but the molecular mechanisms underlying this pulsatility are poorly understood. Oscillations in the intracellular free [ATP]/[ADP] ratio represent one possible mechanism because they would be expected to cause fluctuations in ATP-sensitive K+ channel activity and hence oscillatory Ca2+ influx. After imaging recombinant firefly luciferase, expressed via an adenoviral vector in single human or mouse islet beta-cells, we report here that cytosolic free ATP concentrations oscillate and that these oscillations are affected by glucose. In human beta-cells, oscillations were observed at both 3 and 15 mmol/l glucose, but the oscillations were of a longer wavelength at the higher glucose concentration (167 vs. 66 s). Mouse beta-cells displayed oscillations in both cytosolic free [Ca2+] and [ATP] only at elevated glucose concentrations, both with a period of 120 s. To explore the causal relationship between [Ca2+] and [ATP] oscillations, the regulation of each was further investigated in populations of MIN6 beta-cells. Incubation in Ca2+-free medium lowered cytosolic [Ca2+] but increased [ATP] in MIN6 cells at both 3 and 30 mmol/l glucose. Removal of external Ca2+ increased [ATP], possibly by decreasing ATP consumption by endoplasmic reticulum Ca2+-ATPases. These results allow a model to be constructed of the beta-cell metabolic oscillator that drives nutrient-induced insulin secretion. Diabetes 51 (Suppl. 1): 5162-5170, 2002.