葡萄糖可诱导移植性大鼠胰岛素瘤释放胰岛素并使胞质钙浓度升高。

Glucose induces insulin release and a rise in cytosolic calcium concentration in a transplantable rat insulinoma.

作者信息

Hoenig M, Sharp G W

出版信息

Endocrinology. 1986 Dec;119(6):2502-7. doi: 10.1210/endo-119-6-2502.

Abstract

An important role for calcium in the cellular events leading to insulin secretion is supported by many studies. However, simultaneous measurements of changes in intracellular free Ca2+ concentrations [( Ca2+]i) and insulin release in response to secretagogues have not been performed. Using cells isolated from a glucose-responsive insulinoma, changes in [Ca2+]i were measured with the fluorescent calcium probe quin2. With the nutrient secretagogues glucose (30 mM) and D,L-glyceraldehyde (GA; 20 mM), [Ca2+]i increased slowly, reaching a peak approximately 15 min after addition of the stimulus, while KCl (25 mM) and carbachol (2 mM) led to a rapid but transient increase in [Ca2+]i. Glucose increased [Ca2+]i from 104 +/- 6 (mean +/- SEM) to 248 +/- 31 mM (n = 13), and GA caused a rise in [Ca2+]i from 96 +/- 6 to 280 +/- 39 nM (n = 4). KCl and carbachol caused a rise from 107 +/- 6 to 184 +/- 5 nM and from 98 +/- 5 to 157 +/- 5 nM, respectively (n = 5 each). When insulin release was measured simultaneously with changes in [Ca2+]i and compared to unstimulated cells, the following results were obtained. During the first 5 min of stimulation, high glucose caused a 90 +/- 12% increase in insulin release and a 72 +/- 11% rise in [Ca2+]i (n = 5). GA evoked a 122 +/- 30% increase in insulin secretion, with a 82 +/- 17% rise in [Ca2+]i (n = 3). Both KCl and carbachol caused a 58 +/- 9% increase in insulin release, with 7 +/- 4% and 50 +/- 2% rises in [Ca2+]i, respectively (n = 4 each). Insulin release was also measured in a perifusion system. It was shown that glucose (30 mM), GA (20 mM), and alpha-ketoisocaproate (30 mM) caused a biphasic release of insulin, while KCl (25 mM) and carbachol (2 mM) caused a monophasic release. The results show that [Ca2+]i increases during the stimulation of insulin secretion when measured simultaneously on the same beta-cells. However, while these changes coincide, a simple direct quantitative relationship between insulin release and the rise in [Ca2+]i could not be demonstrated.

摘要

许多研究都支持钙在导致胰岛素分泌的细胞事件中起重要作用。然而，尚未同时测量细胞内游离钙离子浓度([Ca2+]i)的变化以及对促分泌素作出反应时的胰岛素释放情况。使用从葡萄糖反应性胰岛素瘤中分离出的细胞，用荧光钙探针喹啉-2测量[Ca2+]i的变化。对于营养促分泌素葡萄糖(30 mM)和D,L-甘油醛(GA;20 mM)，[Ca2+]i缓慢升高，在添加刺激物后约15分钟达到峰值，而氯化钾(25 mM)和卡巴胆碱(2 mM)导致[Ca2+]i迅速但短暂地升高。葡萄糖使[Ca2+]i从104±6(平均值±标准误)升高到248±31 nM(n = 13)，GA使[Ca2+]i从96±6升高到280±39 nM(n = 4)。氯化钾和卡巴胆碱分别使[Ca2+]i从107±6升高到184±5 nM以及从98±5升高到157±5 nM(n均为5)。当同时测量胰岛素释放和[Ca2+]i的变化并与未受刺激的细胞进行比较时，得到了以下结果。在刺激的前5分钟内，高糖使胰岛素释放增加90±12%，[Ca2+]i升高72±11%(n = 5)。GA使胰岛素分泌增加122±30%，[Ca2+]i升高82±17%(n = 3)。氯化钾和卡巴胆碱均使胰岛素释放增加58±9%，[Ca2+]i分别升高7±4%和50±2%(n均为4)。还在灌流系统中测量了胰岛素释放。结果表明，葡萄糖(30 mM)、GA(20 mM)和α-酮异己酸(30 mM)引起胰岛素双相释放，而氯化钾(25 mM)和卡巴胆碱(2 mM)引起单相释放。结果表明，在同一β细胞上同时测量时胰岛素分泌刺激过程中[Ca2+]i升高。然而，虽然这些变化是同步的，但无法证明胰岛素释放与[Ca2+]i升高之间存在简单的直接定量关系。