Jo Junghyo, Choi Moo Young, Koh Duk-Su
Laboratory of Biological Modeling, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Theor Biol. 2009 Mar 21;257(2):312-9. doi: 10.1016/j.jtbi.2008.12.005. Epub 2008 Dec 11.
Glucose homeostasis is controlled by the islets of Langerhans which are equipped with alpha-cells increasing the blood glucose level, beta-cells decreasing it, and delta-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 alpha-, beta-, and delta-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 alpha- and beta-cells contributes to the dynamic stability while the perturbed glucose level recovers to the normal level. Second, the inhibitory interactions of delta-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 delta-cells. It is thus concluded that the intercellular communications in islets of Langerhans should contribute to the effective control of glucose homeostasis.
葡萄糖稳态由胰岛控制,胰岛中含有可提高血糖水平的α细胞、降低血糖水平的β细胞以及作用仍有待明确的δ细胞。尽管最近观察到了这些内分泌细胞之间的细胞间通讯,但其在葡萄糖稳态中的作用尚未得到清楚理解。在本研究中,我们构建了一个由双态α细胞、β细胞和δ细胞组成的胰岛数学模型,并分析了它们之间已知化学相互作用的影响,重点关注这些相互作用的综合效应。特别地,明确考虑了相邻细胞的旁分泌信号、细胞对外部葡萄糖浓度的细胞间差异以及取决于胰岛素和胰高血糖素激素的葡萄糖动态变化等特征。我们的模型预测了细胞间相互作用的三个可能益处:第一,α细胞和β细胞之间的不对称相互作用有助于动态稳定性,同时使受干扰的葡萄糖水平恢复到正常水平。第二,δ细胞对胰高血糖素和胰岛素分泌的抑制性相互作用可防止它们在正常葡萄糖水平下的浪费性共分泌。最后,由于δ细胞的抑制作用,胰岛素分泌的葡萄糖剂量反应在高葡萄糖水平下被改变得更加明显。因此得出结论,胰岛中的细胞间通讯应有助于有效控制葡萄糖稳态。