Martin F, Sanchez-Andres J V, Soria B
Department of Physiology, University of Alicante, School of Medicine, Spain.
Diabetes. 1995 Mar;44(3):300-5. doi: 10.2337/diab.44.3.300.
The effect of alpha-ketoisocaproate (KIC), the first catabolic metabolite of the amino acid leucine, on [Ca2+]i, insulin release, and membrane potential was measured in mouse pancreatic islets of Langerhans. Stimulatory concentrations of KIC (2.5-10 mmol/l) caused slow oscillations of [Ca2+]i and cyclic variations of the membrane potential. Slow [Ca2+]i oscillations depended on extracellular calcium. Simultaneous measurements of [Ca2+]i and insulin release resolved pulsatile insulin secretion that paralleled slow [Ca2+]i oscillations. Whereas 11 mmol/l glucose induced a significant increase in cAMP, KIC was unable to modify it. Glucagon (10 nmol/l), which significantly increased cAMP in mouse islets, also increased the frequency of glucose-induced fast [Ca2+]i oscillations. However, neither glucagon (10 nmol/l) nor dibutyryl cAMP (1 mmol/l) was able to change the slow oscillation pattern into a fast pattern. Imaging of Ca2+ showed that KIC-induced slow oscillations were synchronic throughout the whole islet. It is suggested that beta-cell electrical activity plays a role in the origin of slow [Ca2+]i oscillations.
在小鼠胰岛中测量了亮氨酸的首个分解代谢产物α-酮异己酸（KIC）对细胞内钙离子浓度（[Ca2+]i）、胰岛素释放和膜电位的影响。刺激浓度的KIC（2.5 - 10 mmol/L）引起[Ca2+]i的缓慢振荡和膜电位的周期性变化。[Ca2+]i的缓慢振荡依赖于细胞外钙。同时测量[Ca2+]i和胰岛素释放发现，脉冲式胰岛素分泌与[Ca2+]i的缓慢振荡平行。虽然11 mmol/L的葡萄糖可显著增加环磷酸腺苷（cAMP），但KIC无法改变它。胰高血糖素（10 nmol/L）可显著增加小鼠胰岛中的cAMP，同时也增加了葡萄糖诱导的快速[Ca2+]i振荡的频率。然而，胰高血糖素（10 nmol/L）和二丁酰环磷腺苷（1 mmol/L）都无法将缓慢振荡模式转变为快速模式。钙离子成像显示，KIC诱导的缓慢振荡在整个胰岛中是同步的。研究表明，β细胞电活动在[Ca2+]i缓慢振荡的起源中起作用。
