Islets of Langerhans consist of a large functional syncytium of beta cells that produce pulses of insulin, a key component for controlling metabolic homeostasis. In response to stimulation, the islet cells display rather well-coordinated intercellular activity patterns, which was found crucial for ensuring normal secretory patterns. However, it is not clear how coordinated cellular rhythmicity emerges within the heterogeneous cellular collectives and how it is altered in diabetes. To address these questions, we combined multicellular calcium imaging in mouse pancreatic tissue slices as well as in isolated human islets with advanced network analyses. Describing the intercellular activity patterns by means of network language has not only revealed that intercellular networks in islets share many architectural similarities with several other real-life networks, such as small-worldness, heterogeneity, and modularity, but also leads to important new insights into the relationship between cellular metabolic activity and the orchestration of collective behaviour [1,2]. Importantly, analyses of islets from diabetic donors have revealed that the intercellular activity in these islets is characterized by a lower fraction of global calcium waves and more segregated network structures [3]. However, there was a rather large variability in responses in islets from donors with diabetes, with some exhibited striking pathophysiological changes, whilst others behaved rather normally. This great heterogeneity in susceptibility of different islets towards diabetogenic insults should be considered as an important aspect by conducting further research on the pancreatic islets.

[1] Gosak M, et al., Network science of biological systems at different scales: A review, Physics of Life Reviews 2018, 24.

[2] Stožer A, et al., From isles of Königsberg to islets of Langerhans: Examining the function of the endocrine pancreas through network science, Frontiers in Endocrinology 2022, 922640.

[3] Gosak M, et al., Ca²⁺ oscillations, waves, and networks in islets from human donors with and without type 2 diabetes, Diabetes 2022, 71.