Unit of Endocrinology and Metabolism, University of Louvain, Faculty of Medicine, B-1200 Brussels, Belgium.
Mol Cell Endocrinol. 2013 Mar 10;367(1-2):11-20. doi: 10.1016/j.mce.2012.12.002. Epub 2012 Dec 11.
Insulin secretion (IS) triggered by β-cell Ca(2+) is amplified by metabolic and receptor-generated signals. Diacylglycerol largely mediates acetylcholine (ACh) effects through protein-kinase C and other effectors, which can be directly activated by phorbol-ester (PMA). Using mouse islets, we investigated the possible role of microfilaments in ACh/PMA-mediated amplification of IS. PMA had no steady-state impact on actin microfilaments. Although ACh slightly augmented and PMA diminished glucose- and tolbutamide-induced increases in β-cell Ca(2+), both amplified IS in control islets and after microfilament disruption (latrunculin) or stabilization (jasplakinolide). Both phases of IS were larger in response to glucose than tolbutamide, although Ca(2+) was lower. This difference in secretion, which reflects metabolic amplification, persisted in presence of ACh/PMA and was independent of microfilaments. Amplification of IS by ACh/PMA is thus distinct from metabolic amplification, but both pathways promote acquisition of release competence by insulin granules, which can access exocytotic sites without intervention of microfilaments.
β 细胞[Ca(2+)]（c）引发的胰岛素分泌（IS）被代谢和受体产生的信号放大。二酰基甘油主要通过蛋白激酶 C 和其他效应物介导乙酰胆碱（ACh）的作用，这些效应物可以被佛波酯（PMA）直接激活。我们使用小鼠胰岛研究了微丝在 ACh/PMA 介导的 IS 放大中的可能作用。PMA 对肌动蛋白微丝没有稳态影响。虽然 ACh 轻微增加，PMA 减少葡萄糖和甲苯磺丁脲诱导的β 细胞[Ca(2+)]（c）增加，但在对照胰岛中和微丝破坏（Latrunculin）或稳定（jasplakinolide）后，均放大 IS。尽管[Ca(2+)]（c）较低，但葡萄糖反应的 IS 两期均大于甲苯磺丁脲。这种分泌差异反映了代谢放大，在 ACh/PMA 存在下仍然存在，并且与微丝无关。因此，ACh/PMA 对 IS 的放大与代谢放大不同，但两种途径都促进胰岛素颗粒获得释放能力，而无需微丝干预即可到达胞吐部位。
