Effects of morphological and functional heterogeneities on the intracellular Ca2+ signals in coupled pancreatic beta cells
Abstract
The Islets of Langerhans are mainly composed of insulin-secreting pancreatic ОІ-cells, glucagon-secreting О±-cells and somatostatin-secreting Оґ-cells[1]. At the cellular level, secretion of these hormones takes place through a common mech- anism involving glucose metabolism, electrical activity and Ca2+-handling[2]. In addition, pancreatic hormone secretion is regulated by intra-islet interactions including paracrine and autocrine signals, as well as electrical coupling mediated by gap junctions between ОІ-cells[3].
Electrical coupling between ОІ-cells has been previously studied both theo- retically and experimentally. In these studies, it was shown that ОІ-cell coupling is essential for the synchronized release of insulin[1]. In addition, it was demon- strated that the lack of functional gap junctions leads to impaired pulsatile insulin secretion due to uncoordinated Ca2+ oscillations[4].
In this work we used a computational model to assess the effect of morpho- logical and functional heterogeneities in the islet ОІ-cells (including differences in cell sizes, ОІ-cell interconnectivity and electrophysiological and Ca2+ buffering properties) on the Ca2+ signal produced in the cytosol, ultimately related to the secretory response of the islet ОІ-cells.
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