PGF_(2α)促进NIT-1β细胞葡萄糖刺激性胰岛素分泌的相关机制研究  

Mechanisms of PGF_ (2α) on the glucose-induced insulin secretion in NIT-1β cells

作　　者：袁振宇[1] 叶春玲[1] 金永亮[1] 孙景波[2] 叶开和[1] 蒋家华[3] 

机构地区：[1]暨南大学药学院药理教研室,广东广州510632 [2]广东省中医院中心实验室,广东广州510120 [3]多伦多大学医学院生理实验室

出　　处：《中国病理生理杂志》2006年第7期1295-1299,共5页Chinese Journal of Pathophysiology

基　　金：广东省自然科学基金资助项目(No.04010463);国家自然科学基金资助项目(No.30070873)

摘　　要：目的:探讨PGF2α促进葡萄糖刺激性胰岛素分泌的作用机制。方法:运用放免方法检测PGF2α在不同情况下对NIT-1β细胞葡萄糖刺激性胰岛素分泌量的变化,并以Fluo-3AM为探针,利用激光共聚焦显微镜检测细胞内钙的改变。结果:在0和5.5mmol/L葡萄糖时,5μmol/L的PGF2α使NIT-1β细胞胰岛素分泌无明显增加;但在16.5mmol/L葡萄糖时,PGF2α明显增加胰岛素分泌(P<0.01);ddA或Ly-83583对PGF2α增强的胰岛素分泌没有显著影响(均P<0.01),预先给予U-73122抑制了PGF2α促进的胰岛素分泌(P<0.01);预先给予calphostinC,PGF2α也不能进一步诱导增强胰岛素的分泌(P<0.05)。另外,PGF2α能够引起β细胞内钙升高,预先给予ddA或Ly-83583,均不能阻断其作用,而预先给予U-73122则抑制了PGF2α引起的β细胞内钙升高。结论:PGF2α增强高浓度葡萄糖刺激下的胰岛素分泌,可能是通过激活PLC双信号途径,诱导细胞内钙升高和激活PKC途径发挥作用。另外,PGF的作用与cAMP/PKA或cGMP/PKG信息通路可能没有关系。AIM ： To investigate the cellular mechanisms by which PGF2α promotes glucose - stimulated insulin secretion in NIT - 1 beta cells. METHODS ： Using the radioimmunoassay （ RIA）, the amount of the PGF2α augmentation of glucose stimulated insulin secession was determined in different conditions, and the confocal laser scanning methods by Fluo - 3AM as a fluorescent probe were used to analyze the changes of intracellular calcium in NIT - 1β cells. RESULTS ： At the lower glucose （0, 5. 5 mmol/L）, PGF2α （5 μmol/L） failed to potentiate insulin secretion （ P 〉 0. 05 ）. However, in the presence of 16. 5 mmol/L glucose, PGF2α increased significantly in insulin secretion （ P 〈 0. 05 ）. Neither the.AC inhibitor ddA nor the GC inhibitor Ly - 83583 altered PGF2α - potentiated insulin secretion in the presence of 16. 5 mmol/L （ P 〈 0. 05 or P 〈0. 01 ）. Otherwise, the PLC inhibitor U -73122 and the PKC blocker calphostin C both counteracted the insulinotropic of PGF2α （ P 〈 0. 01 or P 〈 0. 05 ）. Moreover, exposure of the NIT - 1β cells to 5 μmol/L PGF2α induced a rapid increase of intracellular calcium （ P 〈 0. 01 ）. The inhibitor, ddA or Ly - 83583 had no impact on PGF2α - induced elevation of the intracellular calcium （P 〈 0. 01 ）. Pretreatment of the cells with U -73122 completely prevented the calcium response induced by PGF2α （P 〈0.01 ）. CONCLUSION： Efects of PGF2α was independent of cAMP or cGMP, potentiated glucose （16. 5 mmol/L） -induced insulin secretion in NIT- 1β cells through stimulation of phospholipase C, which subsequently mediated the elevation of intracellular calcium and activation of protein kinase C.

关 键 词：前列腺素F类 胰岛素 NIT-1β细胞 葡萄糖 

分 类 号：R363[医药卫生—病理学]