Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets -: Free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose
Augmentation of Ca2+-stimulated insulin release by glucose and long-chain fatty acids in rat pancreatic islets -: Free fatty acids mimic ATP-sensitive K+ channel-independent insulinotropic action of glucose
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DOI：
10.2337/diabetes.48.8.1543
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发表时间：
1999-08-01
期刊：
影响因子：
7.7
通讯作者：
Aizawa, T
中科院分区：
文献类型：
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作者：
Komatsu, M;Yajima, H;Aizawa, T
葡萄糖以不依赖于atp敏感的KC通道（K-ATP通道）的方式增加Ca2+刺激的胰岛素从胰腺β细胞释放。为了研究这一作用的机制，我们使用大鼠胰岛，研究了外源性游离脂肪酸（FFAs）对kcl诱导的Ca2+刺激的胰岛素释放的影响，FFAs是长链酰基辅酶a （LC-CoA）的前体。肉豆蔻酸盐、棕榈酸盐和硬脂酸盐增强了在2.8 mmol/l葡萄糖存在下，50mmol /l KCl诱导的胰岛素释放。急性添加后，其效力较葡萄糖诱导的增强剂弱。然而，当胰岛在KCl刺激前在严格的无Ca2+条件下（1 mmol/l EGTA）与FFAs预孵育时，ffa诱导的增强变得更大。在这些条件下，16.7 mmol/l葡萄糖能使50 mmol/l KCl诱导的胰岛素释放增加13倍，而棕榈酸盐和肉豆蔻酸盐（游离浓度均为10 mmol/l）能使胰岛素释放增加5.8倍和5.2倍。游离脂肪酸和葡萄糖的作用呈浓度依赖性。11.1 mmol/l葡萄糖和10 mmol/l棕榈酸盐诱导的增强时间分布相似。葡萄糖和棕榈酸盐在刺激前10分钟产生几乎相同的增强模式；随后，葡萄糖增强比棕榈酸增强更持久。这表明存在一个长期的葡萄糖特异性信号片段，它不能被ffa模仿。我们的研究结果提供了直接的证据，证明FFAs可以模拟葡萄糖的K-ATP，通道无关的作用。将这些结果与先前的结果结合起来，我们得出结论，葡萄糖至少在一定程度上通过增加丙二酰辅酶a和细胞质lc -辅酶a来增加Ca2+刺激的胰岛素释放。然而，一个或多个其他葡萄糖特异性信号分子是充分表达增强所必需的。
Glucose augments Ca2+-stimulated insulin release from the pancreatic beta-cell in an ATP-sensitive KC channel (K-ATP channel)-independent manner. In studying the mechanisms underlying this action, we used rat pancreatic islets and examined the effects of exogenous free fatty acids (FFAs), which are precursors of long-chain acyl-CoA (LC-CoA), on KCl-induced Ca2+-stimulated insulin release. Myristate, palmitate, and stearate augmented insulin release induced by 50 mmol/l KCl in the presence of 2.8 mmol/l glucose. Added acutely, their potency was weak compared with that of glucose-induced augmentation. The FFA-induced augmentation became much greater, however, when islets were preincubated with FFAs under stringent Ca2+-free conditions (with 1 mmol/l EGTA) before the KCl stimulation. Under these conditions, 16.7 mmol/l glucose augmented 13-fold insulin release induced by 50 mmol/l KCl, whereas palmitate or myristate (both at a free concentration of 10 mu mol/l) produced 5.8- and 5.2-fold augmentations. Effects of FFAs and glucose were concentration-dependent. The temporal profiles of augmentation induced by 11.1 mmol/l glucose and 10 mu mol/l palmitate were similar. Glucose and palmitate caused almost identical augmentation patterns for the initial 10 min of stimulation; subsequently, glucose augmentation was better sustained than palmitate augmentation. This suggests the existence of a longer-term glucose-specific signaling moiety that cannot be mimicked by FFAs. Our results provide direct evidence that FFAs can mimic the K-ATP, channel-independent action of glucose. Taking these results together with previous results, we conclude that glucose augments Ca2+-stimulated insulin release, at least in part, by increasing malonyl-CoA and cytosolic LC-CoA. However, one or more other glucose-specific signaling molecules are required for the full expression of augmentation.