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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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Characteristics of functional networks of beta cells in 9 islets of Langerhans for three of the five regimes analyzed.A The average correlation coefficient. B The average physical distance between connected cells. C The average node degree. D The average clustering coefficient. E The global efficiency. F the average lengths of connections originating from 20% of the cells with the highest degree. In all panels red circles denote the median values, whereas the yellow floating columns signify the broadness of intervals within which the values were detected in all 9 islets. Significant differences obtained after pairwise post hoc Wilcoxon signed-rank tests are indicated by asterisks.
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pcbi-1002923-g005: Characteristics of functional networks of beta cells in 9 islets of Langerhans for three of the five regimes analyzed.A The average correlation coefficient. B The average physical distance between connected cells. C The average node degree. D The average clustering coefficient. E The global efficiency. F the average lengths of connections originating from 20% of the cells with the highest degree. In all panels red circles denote the median values, whereas the yellow floating columns signify the broadness of intervals within which the values were detected in all 9 islets. Significant differences obtained after pairwise post hoc Wilcoxon signed-rank tests are indicated by asterisks.

Mentions: To describe the average properties of the functional networks (9 datasets) in more detail, we calculated for the LG1, HG, and LG2 regimes the respective average correlation coefficient Ravg (as a reference), the average physical distance between connected cells lij, the average degree kavg, the average clustering coefficient Cavg, the global efficiency Eglob, and the average lengths of connections that originate from 20% of the most connected cells in the slice. Results are presented in Figure 5. Comparisons between regimes were done performing Friedman's ANOVA in the first step and post hoc Wilcoxon signed-rank test in the second to compare LG1 with HG, HG with LG2, and LG1 with LG2. A Bonferroni correction for the number of post hoc pairwise comparisons was applied and so all differences are reported at the level of significance p<0.05/3 = 0.0167. For all 6 parameters the differences between groups were significant. Significant differences obtained after pairwise post hoc comparisons are indicated by asterisks. During HG regime, Ravg was significantly higher than in LG1, lij significantly shorter than in LG2, kavg significantly higher than in LG1, Cavg significantly higher than in either of the LG regimes, further supporting the results obtained so far. To check whether the nodes with the highest degrees connect predominantly to physically close or distant cells, we calculated the average lengths of connections originating from 20% of the cells with the highest degree. The latter were significantly shorter in HG than in LG2. Additionally, by comparing panels B and F it appears that the most connected nodes do not display any preference for either short- or long-range connections in neither of the regimes considered. For Eglob, differences between HG and LG1 and HG and LG2 were not statistically significant (p<0.021 for LG1 vs. HG and p<0.086 for HG vs. LG2), but a trend towards higher efficiency in HG is clearly visible. Notably, the differences between both regimes in low glucose, LG1 and LG2, were never statistically significant, strongly supporting the view that the effect of stimulation was largely reversible.


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)

Characteristics of functional networks of beta cells in 9 islets of Langerhans for three of the five regimes analyzed.A The average correlation coefficient. B The average physical distance between connected cells. C The average node degree. D The average clustering coefficient. E The global efficiency. F the average lengths of connections originating from 20% of the cells with the highest degree. In all panels red circles denote the median values, whereas the yellow floating columns signify the broadness of intervals within which the values were detected in all 9 islets. Significant differences obtained after pairwise post hoc Wilcoxon signed-rank tests are indicated by asterisks.
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002923-g005: Characteristics of functional networks of beta cells in 9 islets of Langerhans for three of the five regimes analyzed.A The average correlation coefficient. B The average physical distance between connected cells. C The average node degree. D The average clustering coefficient. E The global efficiency. F the average lengths of connections originating from 20% of the cells with the highest degree. In all panels red circles denote the median values, whereas the yellow floating columns signify the broadness of intervals within which the values were detected in all 9 islets. Significant differences obtained after pairwise post hoc Wilcoxon signed-rank tests are indicated by asterisks.
Mentions: To describe the average properties of the functional networks (9 datasets) in more detail, we calculated for the LG1, HG, and LG2 regimes the respective average correlation coefficient Ravg (as a reference), the average physical distance between connected cells lij, the average degree kavg, the average clustering coefficient Cavg, the global efficiency Eglob, and the average lengths of connections that originate from 20% of the most connected cells in the slice. Results are presented in Figure 5. Comparisons between regimes were done performing Friedman's ANOVA in the first step and post hoc Wilcoxon signed-rank test in the second to compare LG1 with HG, HG with LG2, and LG1 with LG2. A Bonferroni correction for the number of post hoc pairwise comparisons was applied and so all differences are reported at the level of significance p<0.05/3 = 0.0167. For all 6 parameters the differences between groups were significant. Significant differences obtained after pairwise post hoc comparisons are indicated by asterisks. During HG regime, Ravg was significantly higher than in LG1, lij significantly shorter than in LG2, kavg significantly higher than in LG1, Cavg significantly higher than in either of the LG regimes, further supporting the results obtained so far. To check whether the nodes with the highest degrees connect predominantly to physically close or distant cells, we calculated the average lengths of connections originating from 20% of the cells with the highest degree. The latter were significantly shorter in HG than in LG2. Additionally, by comparing panels B and F it appears that the most connected nodes do not display any preference for either short- or long-range connections in neither of the regimes considered. For Eglob, differences between HG and LG1 and HG and LG2 were not statistically significant (p<0.021 for LG1 vs. HG and p<0.086 for HG vs. LG2), but a trend towards higher efficiency in HG is clearly visible. Notably, the differences between both regimes in low glucose, LG1 and LG2, were never statistically significant, strongly supporting the view that the effect of stimulation was largely reversible.

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