Characterization of Purinergic Receptor-Evoked Increases in Intracellular Ca2+ Transients in Isolated Human and Rodent Insulin-Secreting Cells
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In vivo many factors determine the regulation of insulin secretion from the β-cells of the pancreatic islets of Langerhans. The most predominant influence is a rise in the concentration of plasma glucose, which will promote secretion by mechanisms associated with Ca2+ influx across the plasma membrane(1). Insulin release is also governed by changes in the concentration of circulating amino acids, gastrointestinal hormones, neuropeptides and neurotransmitters. These influences are important avenues for β-cell regulation as they not only provide a link between the gastrointestinal tract and the pancreatic islets — the enteroinsular axis, but they also govern the neurohormonal control of secretion. For many years it has been recognised that extracellular ATP is a potent insulin secretagogue(2). In vitro it has been demonstrated using rodent and clonal insulin-secreting cells that purinergic receptor activation is coupled to an increase in [Ca2+]i(3–6). However, few studies have examined intracellular Ca2+ signalling in isolated human insulin-secreting cells(4,7–10). In a recent paper we have shown that ATP and other agonists of the purinergic receptor evoke marked increases in [Ca2+]i in β-cells isolated from transplantable human islets of Langerhans(11). In this paper we examine: (i) the purinergic receptor subtype present in human tissue, (ii) compare purinergic receptor-evoked increases in [Ca2+]i in both rodent and human β-cells and (iii) demonstrate that intracellular Ca2+ signals can also be recorded in cryopreserved human β-cells originally isolated from cadaver organ donors.
KeywordsRINm5F Cell United Kingdom Introduction Enteroinsular Axis Rodent Tissue Rodent Islet
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