Kelly K L, Laychock S G
Prostaglandins. 1984 Jun;27(6):925-38. doi: 10.1016/s0090-6980(84)80011-8.
Isolated pancreatic islets of the rat were either prelabeled with [3H]arachidonic acid, or were incubated over the short term with the concomitant addition of radiolabeled arachidonic acid and a stimulatory concentration of glucose (17mM) for prostaglandin (PG) analysis. In prelabeled islets, radiolabel in 6-keto-PGF1 alpha, PGE2, and 15-keto-13,14-dihydro-PGF2 alpha increased in response to a 5 min glucose (17mM) challenge. In islets not prelabeled with arachidonic acid, label incorporation in 6-keto-PGF1 alpha increased, whereas label in PGE2 decreased during a 5 min glucose stimulation; after 30-45 min of glucose stimulation labeled PGE levels increased compared to control (2.8mM glucose) levels. Enhanced labelling of PGF2 alpha was not detected in glucose-stimulated islets prelabeled or not. Isotope dilution with endogenous arachidonic acid probably occurs early in the stimulus response in islets not prelabeled. D-Galactose (17mM) or 2-deoxyglucose (17mM) did not alter PG production. Indomethacin inhibited islet PG turnover and potentiated glucose-stimulated insulin release. Islets also converted the endoperoxide [3H]PGH2 to 6-keto-PGF1 alpha, PGF2 alpha, PGE2 and PGD2, in a time-dependent manner and in proportions similar to arachidonic acid-derived PGs. In dispersed islet cells, the calcium ionophore ionomycin, but not glucose, enhanced the production of labeled PGs from arachidonic acid. Insulin release paralleled PG production in dispersed cells, however, indomethacin did not inhibit ionomycin-stimulated insulin release, suggesting that PG synthesis was not required for secretion. In confirmation of islet PGI2 turnover indicated by 6-keto-PGF1 alpha production, islet cell PGI2-like products inhibited platelet aggregation induced by ADP. These results suggest that biosynthesis of specific PGs early in the glucose secretion response may play a modulatory role in islet hormone secretion, and that different pools of cellular arachidonic acid may contribute to PG biosynthesis in the microenvironment of the islet.
将大鼠分离的胰岛用[3H]花生四烯酸预先标记，或者在短期孵育时同时添加放射性标记的花生四烯酸和刺激浓度的葡萄糖（17mM）以进行前列腺素（PG）分析。在预先标记的胰岛中，6-酮-PGF1α、PGE2和15-酮-13,14-二氢-PGF2α中的放射性标记物在5分钟葡萄糖（17mM）刺激后增加。在未用花生四烯酸预先标记的胰岛中，在5分钟葡萄糖刺激期间，6-酮-PGF1α中的标记物掺入增加，而PGE2中的标记物减少；在葡萄糖刺激30 - 45分钟后，与对照（2.8mM葡萄糖）水平相比，标记的PGE水平增加。在预先标记或未预先标记的葡萄糖刺激的胰岛中均未检测到PGF2α的标记增强。在未预先标记的胰岛中，内源性花生四烯酸的同位素稀释可能在刺激反应早期发生。D-半乳糖（17mM）或2-脱氧葡萄糖（17mM）不改变PG的产生。吲哚美辛抑制胰岛PG周转并增强葡萄糖刺激的胰岛素释放。胰岛还以时间依赖性方式并以与花生四烯酸衍生的PG相似的比例将内过氧化物[3H]PGH2转化为6-酮-PGF1α、PGF2α、PGE2和PGD2。在分散的胰岛细胞中，钙离子载体离子霉素而非葡萄糖增强了花生四烯酸产生的标记PG的生成。胰岛素释放与分散细胞中的PG产生平行，然而，吲哚美辛不抑制离子霉素刺激的胰岛素释放，表明分泌不需要PG合成。为了证实由6-酮-PGF1α产生所表明的胰岛PGI2周转，胰岛细胞PGI2样产物抑制ADP诱导的血小板聚集。这些结果表明，葡萄糖分泌反应早期特定PG的生物合成可能在胰岛激素分泌中起调节作用，并且不同的细胞花生四烯酸池可能有助于胰岛微环境中的PG生物合成。
