Beneficial effects of intercellular interactions between pancreatic islet cells in blood glucose regulation

Glucose homeostasis is controlled by the islets of Langerhans which are equipped with αα-cells increasing the blood glucose level, ββ-cells decreasing it, and δδ-cells the precise role of which still needs identifying. Although intercellular communications between these endocrine cells have recently been observed, their roles in glucose homeostasis have not been clearly understood. In this study, we construct a mathematical model for an islet consisting of two-state αα-, ββ-, and δδ-cells, and analyze effects of known chemical interactions between them with emphasis on the combined effects of those interactions. In particular, such features as paracrine signals of neighboring cells and cell-to-cell variations in response to external glucose concentrations as well as glucose dynamics, depending on insulin and glucagon hormone, are considered explicitly. Our model predicts three possible benefits of the cell-to-cell interactions: First, the asymmetric interaction between αα- and ββ-cells contributes to the dynamic stability while the perturbed glucose level recovers to the normal level. Second, the inhibitory interactions of δδ-cells for glucagon and insulin secretion prevent the wasteful co-secretion of them at the normal glucose level. Finally, the glucose dose–responses of insulin secretion is modified to become more pronounced at high glucose levels due to the inhibition by δδ-cells. It is thus concluded that the intercellular communications in islets of Langerhans should contribute to the effective control of glucose homeostasis.