Cunningham B A, Deeney J T, Bliss C R, Corkey B E, Tornheim K
Evans Department of Medicine, Boston University School of Medicine, Massachusetts 02118, USA.
Am J Physiol. 1996 Oct;271(4 Pt 1):E702-10. doi: 10.1152/ajpendo.1996.271.4.E702.
Normal insulin secretion is oscillatory in vivo and from groups of perifused islets. Stimulation of rat islets with different glucose concentrations gave insulin oscillations of similar period (5-8 min) but increasing amplitude. It has been assumed that oscillatory secretion is due to oscillations in intracellular free Ca2+, as seen in single islets and single pancreatic beta-cells. However, when islets were perifused with diazoxide and high KCl to maintain high intracellular free Ca2+, insulin oscillations of similar amplitude and period still occurred on glucose stimulation, although superimposed on elevated basal secretion. Several likely possibilities for a diffusible synchronizing factor were tested, including pyruvate, lactate, ATP, and insulin itself; nevertheless, perifusion with high concentrations of these did not prevent insulin oscillations. Clonal pancreatic beta-cells (HIT) and dissociated islets also exhibited oscillatory insulin secretion, but with the 5- to 8-min period oscillations superimposed on 15- to 20-min period oscillations. These results indicate that the mechanisms for generating and synchronizing insulin oscillations reside in the beta-cell, although the structure of the islet may modulate the oscillation pattern.
正常胰岛素分泌在体内以及从成组的灌流胰岛中是呈振荡性的。用不同葡萄糖浓度刺激大鼠胰岛会产生相似周期（5 - 8分钟）但振幅增加的胰岛素振荡。据推测，振荡性分泌是由于细胞内游离Ca2+的振荡，这在单个胰岛和单个胰腺β细胞中可见。然而，当用二氮嗪和高钾对胰岛进行灌流以维持高细胞内游离Ca2+时，尽管基础分泌升高，但在葡萄糖刺激下仍会出现相似振幅和周期的胰岛素振荡。对几种可能的可扩散同步因子进行了测试，包括丙酮酸、乳酸、ATP和胰岛素本身；然而，用高浓度的这些物质进行灌流并不能阻止胰岛素振荡。克隆的胰腺β细胞（HIT）和分离的胰岛也表现出振荡性胰岛素分泌，但5至8分钟周期的振荡叠加在15至20分钟周期的振荡之上。这些结果表明，产生和同步胰岛素振荡的机制存在于β细胞中，尽管胰岛的结构可能会调节振荡模式。
