Insulin release induced by nonglucose secretagogues is initiated from beta-cell by a wide variety of stimuli through specific receptors or binding sites. Activation of receptors in turn generates or enhances the cytosol levels of cAMP, cADPR, IP3, DAG, and AA. These second messengers then activate protein kinases, change the ion currents cross the cell membrane, and mobilize intracellular Ca2+, thereby increasing phosphorylated proteins in the cytosol and augmenting [Ca2+]i. These events trigger exocytotic discharge of insulin. The crucial steps in receptor-mediated stimulation-secretion coupling and their relationship to glucose-stimulated insulin release is summarized in Figure 1. At the present stage of research, the general processes of secretagogue binding to receptors, of generating second messengers, of activating several types of protein kinase, and of altering the membrane potential as well as cytosol calcium levels has been intensively studied and qualitatively clarified. However, we know little about the exact nature of substrates of different protein kinases and their function in the insulin secretion process. With the help of molecular biology and protein chemistry, we expect that this gap will be filled in the near future.

中文翻译：

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非葡萄糖胰岛素促分泌剂的作用机理。

非葡萄糖促分泌素诱导的胰岛素释放是由β细胞通过各种刺激通过特定的受体或结合位点引发的。受体的激活反过来会产生或增强cAMP，cADPR，IP3，DAG和AA的细胞溶质水平。然后，这些第二信使激活蛋白激酶，改变穿过细胞膜的离子流，并动员细胞内Ca2 +，从而增加细胞溶胶中的磷酸化蛋白并增加[Ca2 +] i。这些事件触发胰岛素的胞吐。图1总结了受体介导的刺激-分泌偶联的关键步骤及其与葡萄糖刺激的胰岛素释放的关系。在目前的研究阶段，促分泌素与受体结合，产生第二信使的一般过程，关于激活多种类型的蛋白激酶的方法，以及改变膜电位以及细胞溶胶钙水平的方法，已经进行了深入研究和定性分析。但是，我们对不同蛋白激酶的底物的确切性质及其在胰岛素分泌过程中的功能了解甚少。在分子生物学和蛋白质化学的帮助下，我们预计这一差距将在不久的将来得到填补。