Acetylcholine (ACh), the major parasympathetic neurotransmitter, is released by intrapancreatic nerve endings during the preabsorptive and absorptive phases of feeding. In beta-cells, ACh binds to muscarinic M(3) receptors and exerts complex effects, which culminate in an increase of glucose (nutrient)-induced insulin secretion. Activation of PLC generates diacylglycerol. Activation of PLA(2) produces arachidonic acid and lysophosphatidylcholine. These phospholipid-derived messengers, particularly diacylglycerol, activate PKC, thereby increasing the efficiency of free cytosolic Ca(2+) concentration ([Ca(2+)](c)) on exocytosis of insulin granules. IP3, also produced by PLC, causes a rapid elevation of [Ca(2+)](c) by mobilizing Ca(2+) from the endoplasmic reticulum; the resulting fall in Ca(2+) in the organelle produces a small capacitative Ca(2+) entry. ACh also depolarizes the plasma membrane of beta-cells by a Na(+)- dependent mechanism. When the plasma membrane is already depolarized by secretagogues such as glucose, this additional depolarization induces a sustained increase in [Ca(2+)](c). Surprisingly, ACh can also inhibit voltage-dependent Ca(2+) channels and stimulate Ca(2+) efflux when [Ca(2+)](c) is elevated. However, under physiological conditions, the net effect of ACh on [Ca(2+)](c) is always positive. The insulinotropic effect of ACh results from two mechanisms: one involves a rise in [Ca(2+)](c) and the other involves a marked, PKC-mediated increase in the efficiency of Ca(2+) on exocytosis. The paper also discusses the mechanisms explaining the glucose dependence of the effects of ACh on insulin release.

中文翻译：

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胆碱能控制胰腺β细胞功能的机制和生理意义。

乙酰胆碱（ACh）是主要的副交感神经递质，在进食的前吸收期和吸收期由胰内神经末梢释放。在β细胞中，ACh结合毒蕈碱M（3）受体并发挥复杂的作用，最终导致葡萄糖（营养素）诱导的胰岛素分泌增加。PLC的激活产生二酰基甘油。PLA（2）的激活产生花生四烯酸和溶血磷脂酰胆碱。这些磷脂衍生的信使，特别是二酰基甘油，激活PKC，从而提高了胰岛素颗粒的胞吐作用时游离胞质Ca（2+）浓度（[Ca（2 +）]（c））的效率。IP3也由PLC产生，通过从内质网中移动Ca（2+）引起[Ca（2 +）]（c）的快速升高；导致细胞器中Ca（2+）的下降会产生小的电容性Ca（2+）条目。ACh还通过Na（+）依赖性机制使β细胞的质膜去极化。当质膜已经被促分泌剂（例如葡萄糖）去极化时，这种额外的去极化诱导[Ca（2 +）]（c）的持续增加。出人意料的是，当[Ca（2 +）]（c）升高时，ACh还可以抑制电压依赖性Ca（2+）通道并刺激Ca（2+）外排。但是，在生理条件下，乙酰胆碱对[Ca（2 +）]（c）的净作用始终是积极的。ACh的促胰岛素作用来自两种机制：一种涉及[Ca（2 +）]（c）的升高，另一种涉及PKC介导的Ca（2+）对胞吐作用效率的显着提高。