Functional Connectivity in Islets of Langerhans from Mouse Pancreas Tissue Slices

We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Obtained functional networks are analyzed in the light of known structural and physiological properties of islets. Focusing on the temporal evolution of the network under stimulation with glucose, we show that the dynamics are more correlated under stimulation than under non-stimulated conditions and that the highest overall correlation, largely independent of Euclidean distances between cells, is observed in the activation and deactivation phases when cells are driven by the external stimulus. Moreover, we find that the range of interactions in networks during activity shows a clear dependence on the Euclidean distance, lending support to previous observations that beta cells are synchronized via calcium waves spreading throughout islets. Most interestingly, the functional connectivity patterns between beta cells exhibit small-world properties, suggesting that beta cells do not form a homogeneous geometric network but are connected in a functionally more efficient way. Presented results provide support for the existing knowledge of beta cell physiology from a network perspective and shed important new light on the functional organization of beta cell syncitia whose structural topology is probably not as trivial as believed so far.
Author Summary Complex network theory has provided new tools for studying the structure and function of complex systems. A particularly attractive avenue in this context is the analysis of biological systems, since structural principles of complex networks have been identified at all scales of functioning of living organisms. In the present paper, we propose a construction of a complex network representation of pancreatic islets of Langerhans. In this microorgan, interconnected beta cells produce and secrete insulin, an anabolic hormone that controls the level of nutrients in the blood. We determine the functional connectivity on the basis of patterns of correlations between experimentally measured calcium dynamics in individual beta cells. The extracted pattern of pairwise interactions between network elements, i.e. beta cells, is then scrutinized with conventional tools for network analysis. Our findings are largely reconcilable with known structural and functional properties but also point to the presence of unexpected small-world attributes that appear to represent a general organizational principle of the functional connectivity between beta cells. We argue that complex network analysis applied to islets of Langerhans is a valuable new tool in the physiologist's analytical repertoire, and in the future it could help deepen our understanding of their physiology.