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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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2D histograms showing the distribution of pairs of cells with regard to their Euclidean distance lij and correlation coefficient Rij.From left to right, histograms illustrating the distribution in low glucose before stimulation (A), during activation (B), during sustained activity in high glucose (C), during deactivation (D), and in low glucose after stimulation (E) are presented. The color profile is linear and the same in all panels. Blue depicts 0 and red 520 pairs of connected cells in a given interval.
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pcbi-1002923-g003: 2D histograms showing the distribution of pairs of cells with regard to their Euclidean distance lij and correlation coefficient Rij.From left to right, histograms illustrating the distribution in low glucose before stimulation (A), during activation (B), during sustained activity in high glucose (C), during deactivation (D), and in low glucose after stimulation (E) are presented. The color profile is linear and the same in all panels. Blue depicts 0 and red 520 pairs of connected cells in a given interval.

Mentions: To find out whether network analysis can provide evidence for [Ca2+]i waves as the mechanistic substrate of beta cell synchronization, we examined the relationship between the Euclidean distances lij between beta cells and their dynamical correlations in more detail, by making use of 2D binning. More specifically, we calculated the number of cell pairs which fell within a given range of lij and Rij. 2D histograms shown in Figure 3 reveal that in the HG regime there is a strong tendency of nearby cells to be much better correlated with each other than with the remote ones. Interestingly, in none of the other regimes a similarly convincing trend could be noticed.


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)

2D histograms showing the distribution of pairs of cells with regard to their Euclidean distance lij and correlation coefficient Rij.From left to right, histograms illustrating the distribution in low glucose before stimulation (A), during activation (B), during sustained activity in high glucose (C), during deactivation (D), and in low glucose after stimulation (E) are presented. The color profile is linear and the same in all panels. Blue depicts 0 and red 520 pairs of connected cells in a given interval.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002923-g003: 2D histograms showing the distribution of pairs of cells with regard to their Euclidean distance lij and correlation coefficient Rij.From left to right, histograms illustrating the distribution in low glucose before stimulation (A), during activation (B), during sustained activity in high glucose (C), during deactivation (D), and in low glucose after stimulation (E) are presented. The color profile is linear and the same in all panels. Blue depicts 0 and red 520 pairs of connected cells in a given interval.
Mentions: To find out whether network analysis can provide evidence for [Ca2+]i waves as the mechanistic substrate of beta cell synchronization, we examined the relationship between the Euclidean distances lij between beta cells and their dynamical correlations in more detail, by making use of 2D binning. More specifically, we calculated the number of cell pairs which fell within a given range of lij and Rij. 2D histograms shown in Figure 3 reveal that in the HG regime there is a strong tendency of nearby cells to be much better correlated with each other than with the remote ones. Interestingly, in none of the other regimes a similarly convincing trend could be noticed.

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