Calcium Signaling in the Islets

Abstract

Easy access to rodent insulinoma cells and rodent islets and the ease of measuring Ca 2+ by fluorescent indicators have resulted in an overflow of data that have clarified 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 influenced by 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 contributions. Several channels belonging to the transient receptor potential (TRP) family are present in the β-cells. Intracellular Ca 2+ channels and Ca 2+ -induced Ca 2+ release (CICR) add new dimension to the complexity of Ca 2+ signaling in the human β-cells. While a lot more remains to be learnt about the mechanisms of generation and decoding of Ca 2+ signals, much de-learning will also be needed. Human β-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 ~ −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+ ]i changes, whose roles in mediating pulsatile secretion of insulin remain unclear. Future studies need to be directed toward a better understanding of Ca 2+ signaling in the human islet cells in the context of the pathogenesis, prevention, and treatment of human diabetes.