Zawalich W S, Zawalich K C
Yale University School of Nursing, New Haven, CT 06536-0740.
Mol Cell Endocrinol. 1991 Dec;82(2-3):303-11. doi: 10.1016/0303-7207(91)90044-s.
The monokine interleukin-1 alpha (IL-1) induces a glucose-dependent increase in insulin secretion, an effect tentatively attributed to its ability to increase beta cell phosphoinositide (PI) hydrolysis. In the present experiments, the effects of the protein kinase C inhibitor staurosporine (20 nM), the calcium channel antagonist nitrendipine (5 microM), and the diacylglycerol kinase inhibitor monooleoylglycerol (MOG, 25 microM) on 40 nM IL-1-induced increments in insulin release from perifused islets and inositol phosphate levels in [3H]inositol prelabeled islets were assessed. In perifused islets, insulin secretion in response to IL-1 in the presence of 7 mM glucose averaged 313 +/- 43 pg/islet/min 35-40 min after the onset of stimulation. Release from control islets perifused in the presence of 7 mM glucose alone averaged 56 +/- 6 pg/islet/min at this time point. The addition of staurosporine together with IL-1 reduced insulin secretion at this time point to 88 +/- 21 pg/islet/min. This level of IL-1 caused significant increases in inositol phosphate accumulation in the presence of 7 mM glucose but not 2.75 mM glucose. Staurosporine was without a significant effect on inositol phosphate accumulation in response to the monokine. In contrast, nitrendipine (5 microM) inhibited insulin release and inositol phosphate accumulation in a parallel fashion. Finally, MOG significantly amplified release to the monokine without significantly affecting its impact on inositol phosphate accumulation. Nitrendipine or staurosporine blocked this amplifying effect of MOG on secretion. These results emphasize the role of PI hydrolysis in IL-1-induced insulin secretion and suggest further that calcium influx is essential for IL-1 to fully activate both PI hydrolysis and insulin secretion.
单核因子白细胞介素 -1α（IL -1）可诱导胰岛素分泌呈葡萄糖依赖性增加，这一效应暂时归因于其增加β细胞磷酸肌醇（PI）水解的能力。在本实验中，评估了蛋白激酶C抑制剂星形孢菌素（20 nM）、钙通道拮抗剂尼群地平（5 μM）和二酰基甘油激酶抑制剂单油酰甘油（MOG，25 μM）对40 nM IL -1诱导的从灌流胰岛释放胰岛素增加以及[3H]肌醇预标记胰岛中肌醇磷酸水平的影响。在灌流胰岛中，在7 mM葡萄糖存在下，刺激开始后35 - 40分钟，对IL -1作出反应的胰岛素分泌平均为313±43 pg/胰岛/分钟。此时，仅在7 mM葡萄糖存在下灌流的对照胰岛释放量平均为56±6 pg/胰岛/分钟。与IL -1一起添加星形孢菌素可使此时的胰岛素分泌降至88±21 pg/胰岛/分钟。在7 mM葡萄糖而非2.75 mM葡萄糖存在下，这种水平的IL -1会导致肌醇磷酸积累显著增加。星形孢菌素对单核因子诱导的肌醇磷酸积累无显著影响。相比之下，尼群地平（5 μM）以平行方式抑制胰岛素释放和肌醇磷酸积累。最后，MOG显著增强了对单核因子的释放，但对其对肌醇磷酸积累的影响无显著影响。尼群地平或星形孢菌素阻断了MOG对分泌的这种增强作用。这些结果强调了PI水解在IL -1诱导的胰岛素分泌中的作用，并进一步表明钙内流对于IL -1充分激活PI水解和胰岛素分泌至关重要。
