Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Research Center, 118 83 Stockholm, Sweden.
Adv Exp Med Biol. 2010;654:235-59. doi: 10.1007/978-90-481-3271-3_11.
Easy access to rodent islets and insulinoma cells and the ease of measuring Ca(2+) by fluorescent indicators have resulted in an overflow of data that have clarified minute details of Ca(2+) signaling in the rodent islets. Our understanding of the mechanisms and the roles of Ca(2+) signaling in the human islets, under physiological conditions, has been hugely influenced by uncritical extrapolation of the rodent data obtained under suboptimal experimental conditions. More recently, electrophysiological and Ca(2+) studies have elucidated the ion channel repertoire relevant for Ca(2+) signaling in the human islets and have examined their relative importance. Many new channels belonging to the transient receptor potential (TRP) family are present in the beta-cells. Ryanodine receptors, nicotinic acid adenine dinucleotide phosphate channel, and Ca(2+)-induced Ca(2+) release add new dimension to the complexity of Ca(2+) signaling in the human beta-cells. A lot more needs to be learnt about the roles of these new channels and CICR, not because that will be easy but because that will be difficult. Much de-learning will also be needed. Human beta-cells do not have a resting state in the normal human body even under physiological fasting conditions. Their membrane potential under physiologically relevant resting conditions is approximately -50 mV. Biphasic insulin secretion is an experimental epiphenomenon unrelated to the physiological pulsatile insulin secretion into the portal vein in the human body. Human islets show a wide variety of electrical activities and patterns of Ca(2+) changes, whose roles in mediating pulsatile secretion of insulin into the portal vein remain questionable. Future studies will hopefully be directed toward a better understanding of Ca(2+) signaling in the human islets in the context of the pathogenesis and treatment of human diabetes.
啮齿动物胰岛和胰岛素瘤细胞易于获取，并且荧光指示剂易于测量 Ca(2+)，这导致了大量数据的涌现，这些数据阐明了 Ca(2+)信号在啮齿动物胰岛中的细微细节。在生理条件下，我们对人类胰岛中 Ca(2+)信号的机制和作用的理解受到了在次优实验条件下获得的啮齿动物数据的批判性推断的极大影响。最近，电生理学和 Ca(2+)研究阐明了与人类胰岛中 Ca(2+)信号相关的离子通道谱，并研究了它们的相对重要性。许多属于瞬时受体电位 (TRP)家族的新通道存在于β细胞中。Ryanodine 受体、烟酰胺腺嘌呤二核苷酸磷酸通道和 Ca(2+)诱导的 Ca(2+)释放为人类β细胞中 Ca(2+)信号的复杂性增添了新的维度。需要更多地了解这些新通道和 CICR 的作用，这不是因为这很容易，而是因为这很困难。还需要更多的去学习。即使在生理禁食条件下，正常人体中的人类β细胞也没有静止状态。在生理相关的静止条件下，它们的膜电位约为 -50 mV。双相胰岛素分泌是一种实验上的偶发现象，与人体门静脉中生理性脉冲式胰岛素分泌无关。人类胰岛表现出多种电活动和 Ca(2+)变化模式，其在介导门静脉中脉冲式胰岛素分泌中的作用仍存在疑问。未来的研究有望针对人类胰岛中 Ca(2+)信号在人类糖尿病的发病机制和治疗方面的更好理解。
