Functional connectivity in islets of Langerhans from mouse pancreas tissue slices

PLoS Comput Biol. 2013;9(2):e1002923. doi: 10.1371/journal.pcbi.1002923. Epub 2013 Feb 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / analysis*
  • Calcium / metabolism*
  • Calcium Signaling / physiology*
  • Cluster Analysis
  • Computational Biology / methods*
  • Histocytochemistry
  • Islets of Langerhans / cytology*
  • Islets of Langerhans / metabolism*
  • Mice
  • Microscopy, Confocal
  • Models, Biological
  • Systems Theory

Substances

  • Calcium

Grant support

This work was supported by the Slovenian Research Agency Program P3-0310-2334, grant J1―4055, and Grant J3-2290-2334, MPG Partner Group Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.