Calcium signaling in the islets.
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+)](i) 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.
Islam
M Shahidul
MS
Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, Research Center, 118 83 Stockholm, Sweden. shaisl@ki.se
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D003920:Diabetes Mellitus / Q000378:metabolism; D004594:Electrophysiology / Q000379:methods; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology; D007515:Islets of Langerhans / Q000378:metabolism*; D008564:Membrane Potentials; D008954:Models, Biological; D009991:Oscillometry; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D015398:Signal Transduction
D007328:Insulin; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium