The islets of Langerhans exist as a multicellular network that is important for the regulation of blood glucose levels. The majority of cells in the islet are insulin-producing β-cells, which are excitable cells that are electrically coupled via gap junction channels. β-cells have long been known to display heterogeneous functionality. However, due to gap junction electrical coupling, β-cells show coordinated [Ca2+] oscillations when stimulated with glucose, and global quiescence when unstimulated. Small subpopulations of highly functional β-cells have been suggested to control the dynamics of [Ca2+] and insulin release across the islet. In this study, we investigated the theoretical basis of whether small subpopulations of β-cells can disproportionality control islet [Ca2+] dynamics. Using a multicellular model of the islet, we generated continuous or bimodal distributions of β-cell heterogeneity and examined how islet [Ca2+] dynamics depended on the presence of cells with increased excitability or increased oscillation frequency. We found that the islet was susceptible to marked suppression of [Ca2+] when a ~10% population of cells with high metabolic activity was hyperpolarized; where hyperpolarizing cells with normal metabolic activity had little effect. However, when these highly metabolic cells were removed from the islet model, near normal [Ca2+] remained. Similarly, when ~10% of cells with either the highest frequency or earliest elevations in [Ca2+] were removed from the islet, the [Ca2+] oscillation frequency remained largely unchanged. Overall these results indicate that small populations of β-cells with either increased excitability or increased frequency, or signatures of [Ca2+] dynamics that suggest such properties, are unable to disproportionately control islet-wide [Ca2+] via gap junction coupling. As such, we need to reconsider the physiological basis for such small β-cell populations or the mechanism by which they may be acting to control normal islet function.

中文翻译：

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β细胞的小亚群不会通过间隙连接通讯驱动胰岛振荡[Ca2 +]动态

Langerhans的胰岛以多细胞网络的形式存在，对调节血糖水平非常重要。胰岛中的大多数细胞是产生胰岛素的β细胞，它们是通过间隙连接通道电耦合的可激发细胞。长期以来，人们已经知道β细胞会表现出不同的功能。但是，由于间隙连接的电耦合，当用葡萄糖刺激时，β细胞显示出协调的[Ca2 +]振荡，而当不刺激时，则显示出整体静止。有人建议将功能强大的β细胞的小亚群控制在整个胰岛中[Ca2 +]和胰岛素释放的动力学。在这项研究中，我们研究了小数目的β细胞亚群是否可以不成比例地控制胰岛[Ca2 +]动态的理论基础。使用胰岛的多细胞模型，我们生成了β细胞异质性的连续或双峰分布，并研究了胰岛[Ca2 +]动力学如何取决于兴奋性增加或振荡频率增加的细胞的存在。我们发现，当〜10％的具有高代谢活性的细胞超极化时，胰岛很容易受到[Ca2 +]的显着抑制。具有正常代谢活性的超极化细胞几乎没有作用。但是，当这些高代谢细胞从胰岛模型中移出后，仍保留了接近正常的[Ca2 +]。同样，当从胰岛中去除[Ca2 +]中频率最高或最早升高的细胞的约10％时，[Ca2 +]振荡频率基本保持不变。总体而言，这些结果表明，兴奋性或频率增加的β细胞数量很少，或暗示此类性质的[Ca2 +]动力学特征不能通过间隙连接偶联过分地控制胰岛范围内的[Ca2 +]。因此，我们需要重新考虑这些小的β细胞群体的生理基础，或它们可能起着控制正常胰岛功能的机制。