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

• Published in: Journal of theoretical biology 2009-03, Vol.257 (2), p.312-319
• Main Authors: Jo, Junghyo, Choi, Moo Young, Koh, Duk-Su
• Format: Article
• Language: English
• Subjects: Animals; Blood Glucose - metabolism; Diabetes; Feedback; Glucagon-Secreting Cells - drug effects; Glucagon-Secreting Cells - metabolism; Glucose - pharmacology; Glucose homeostasis; Homeostasis - drug effects; Insulin-Secreting Cells - drug effects; Insulin-Secreting Cells - metabolism; Islets of Langerhans; Models, Biological; Paracrine Communication; Somatostatin-Secreting Cells - drug effects; Somatostatin-Secreting Cells - metabolism
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2008.12.005

Glucose homeostasis is controlled by the islets of Langerhans which are equipped with α -cells increasing the blood glucose level, β -cells decreasing it, and δ -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 α -, β -, and δ -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 α - and β -cells contributes to the dynamic stability while the perturbed glucose level recovers to the normal level. Second, the inhibitory interactions of δ -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 δ -cells. It is thus concluded that the intercellular communications in islets of Langerhans should contribute to the effective control of glucose homeostasis.