Tengholm Anders, Gylfe Erik
Department of Medical Cell Biology, Uppsala University, Biomedical Centre, Box 571, SE-75123 Uppsala, Sweden.
Mol Cell Endocrinol. 2009 Jan 15;297(1-2):58-72. doi: 10.1016/j.mce.2008.07.009. Epub 2008 Jul 26.
Pancreatic beta-cells possess an inherent ability to generate oscillatory signals that trigger insulin release. Coordination of the secretory activity among beta-cells results in pulsatile insulin secretion from the pancreas, which is considered important for the action of the hormone in the target tissues. This review focuses on the mechanisms underlying oscillatory control of insulin secretion at the level of the individual beta-cell. Recent studies have demonstrated that oscillations of the cytoplasmic Ca(2+) concentration are synchronized with oscillations in beta-cell metabolism, intracellular cAMP concentration, phospholipase C activity and plasma membrane phosphoinositide lipid concentrations. There are complex interdependencies between the different messengers and signalling pathways that contribute to amplitude regulation and shaping of the insulin secretory response to nutrient stimuli and neurohormonal modulators. Several of these pathways may be important pharmacological targets for improving pulsatile insulin secretion in type 2 diabetes.
胰腺β细胞具有产生触发胰岛素释放的振荡信号的内在能力。β细胞之间分泌活动的协调导致胰腺呈脉冲式分泌胰岛素，这被认为对该激素在靶组织中的作用很重要。本综述聚焦于单个β细胞水平上胰岛素分泌振荡控制的潜在机制。最近的研究表明，细胞质Ca(2+)浓度的振荡与β细胞代谢、细胞内cAMP浓度、磷脂酶C活性及质膜磷酸肌醇脂质浓度的振荡同步。不同信使和信号通路之间存在复杂的相互依存关系，这些关系有助于调节胰岛素对营养刺激和神经激素调节剂分泌反应的幅度及形成其形态。这些通路中的若干条可能是改善2型糖尿病中脉冲式胰岛素分泌的重要药理学靶点。
