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Functional connectivity in islets of Langerhans from mouse pancreas tissue slices.

Stožer A, Gosak M, Dolenšek J, Perc M, Marhl M, Rupnik MS, Korošak D - PLoS Comput. Biol. (2013)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia.

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.

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Related in: MedlinePlus

Cumulative degree distributions of functional networks for three of the five regimes analyzed.Values obtained from all 9 islets are plotted in different colors and the larger black circles indicate their average for low glucose prior to stimulation (A), high glucose (B), and low glucose after stimulation (C). The node degree distributions decay roughly linearly before a drop-off in the tail, thereby indicating a broad-scale nature of the networks.
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pcbi-1002923-g006: Cumulative degree distributions of functional networks for three of the five regimes analyzed.Values obtained from all 9 islets are plotted in different colors and the larger black circles indicate their average for low glucose prior to stimulation (A), high glucose (B), and low glucose after stimulation (C). The node degree distributions decay roughly linearly before a drop-off in the tail, thereby indicating a broad-scale nature of the networks.

Mentions: To determine the scale of our networks we plotted the cumulative degree distribution (Figure 6). In order to be able to combine data from 9 islets with different numbers of responsive cells, we normalized k of each cell to the maximal node degree kmax in the respective islet. In this manner we obliterated the effect of different network sizes and resulting maximal degrees and were thus able to focus on the shape of the distribution only. We drew the cumulative distributions for all 9 islets and three of the five regimes (LG1, HG and LG2), which were then averaged (dark circles). It can be observed that in all three regimes the averaged values decay roughly linearly in the double logarithmic plot before a drop-off in the tail. These results indicate that the functional connectivity between beta cells displays a broad-scale nature. Namely, such connectivity distributions are characterized by a power-law regime followed by a sharp cutoff [9]. To quantify this visual evaluation, we fitted the data with three possible models: a power-law, an exponential decay and an exponentially decaying power-law. Goodness-of-fit was tested using the coefficient of determination r2, whereby a better fit is indicated by a value closer to 1. Of all three model functions, the exponentially truncated power law was the best-fitting model for the cumulative degree distributions in all three regimes. It gave r2 values of 0.99, 0.99 and 0.98 for the LG1, HG and LG2 regime, respectively. The other two fitting options yielded r2 values ranging from 0.8 to 0.98, thus validating that the observed degree distributions are best described by truncated power-laws which is a characteristic of broad-scale networks.


Functional connectivity in islets of Langerhans from mouse pancreas tissue slices.

Stožer A, Gosak M, Dolenšek J, Perc M, Marhl M, Rupnik MS, Korošak D - PLoS Comput. Biol. (2013)

Cumulative degree distributions of functional networks for three of the five regimes analyzed.Values obtained from all 9 islets are plotted in different colors and the larger black circles indicate their average for low glucose prior to stimulation (A), high glucose (B), and low glucose after stimulation (C). The node degree distributions decay roughly linearly before a drop-off in the tail, thereby indicating a broad-scale nature of the networks.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3585390&req=5

pcbi-1002923-g006: Cumulative degree distributions of functional networks for three of the five regimes analyzed.Values obtained from all 9 islets are plotted in different colors and the larger black circles indicate their average for low glucose prior to stimulation (A), high glucose (B), and low glucose after stimulation (C). The node degree distributions decay roughly linearly before a drop-off in the tail, thereby indicating a broad-scale nature of the networks.
Mentions: To determine the scale of our networks we plotted the cumulative degree distribution (Figure 6). In order to be able to combine data from 9 islets with different numbers of responsive cells, we normalized k of each cell to the maximal node degree kmax in the respective islet. In this manner we obliterated the effect of different network sizes and resulting maximal degrees and were thus able to focus on the shape of the distribution only. We drew the cumulative distributions for all 9 islets and three of the five regimes (LG1, HG and LG2), which were then averaged (dark circles). It can be observed that in all three regimes the averaged values decay roughly linearly in the double logarithmic plot before a drop-off in the tail. These results indicate that the functional connectivity between beta cells displays a broad-scale nature. Namely, such connectivity distributions are characterized by a power-law regime followed by a sharp cutoff [9]. To quantify this visual evaluation, we fitted the data with three possible models: a power-law, an exponential decay and an exponentially decaying power-law. Goodness-of-fit was tested using the coefficient of determination r2, whereby a better fit is indicated by a value closer to 1. Of all three model functions, the exponentially truncated power law was the best-fitting model for the cumulative degree distributions in all three regimes. It gave r2 values of 0.99, 0.99 and 0.98 for the LG1, HG and LG2 regime, respectively. The other two fitting options yielded r2 values ranging from 0.8 to 0.98, thus validating that the observed degree distributions are best described by truncated power-laws which is a characteristic of broad-scale networks.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia.

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.

Show MeSH
Related in: MedlinePlus