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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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Correlation matrices R (upper row, images A1–A5) and network architectures (lower row, images B1–B5) for all regimes considered in this study.Upper row: correlation matrices for low glucose before stimulation (A1), activation (A2), sustained activity in high glucose (A3), deactivation (A4), and low glucose after stimulation (A5). The color mapping is linear, values of  = 0.0 and  = 1.0 depicted in blue and red, respectively. Lower row: network architectures for low glucose before stimulation (B1), activation (B2), sustained activity in high glucose (B3), deactivation (B4) and low glucose after stimulation (B5). Each red dot represents the physical position of a nucleus of a glucose glucose-responsive cell inside the islet of Langerhans. Dashed lines correspond to cell outlines. Pairs of cells whose correlation exceeds Rth = 0.75 are connected with an arrow. In addition, colors of arrows signify values of Rij: linear coding between 0.75 (yellow) and 1 (dark brown).
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pcbi-1002923-g002: Correlation matrices R (upper row, images A1–A5) and network architectures (lower row, images B1–B5) for all regimes considered in this study.Upper row: correlation matrices for low glucose before stimulation (A1), activation (A2), sustained activity in high glucose (A3), deactivation (A4), and low glucose after stimulation (A5). The color mapping is linear, values of  = 0.0 and  = 1.0 depicted in blue and red, respectively. Lower row: network architectures for low glucose before stimulation (B1), activation (B2), sustained activity in high glucose (B3), deactivation (B4) and low glucose after stimulation (B5). Each red dot represents the physical position of a nucleus of a glucose glucose-responsive cell inside the islet of Langerhans. Dashed lines correspond to cell outlines. Pairs of cells whose correlation exceeds Rth = 0.75 are connected with an arrow. In addition, colors of arrows signify values of Rij: linear coding between 0.75 (yellow) and 1 (dark brown).

Mentions: We first calculated the linear correlation coefficient between all pairs of N = 140 cells from a single islet of Langerhans, whose average [Ca2+]i response was shown in Figure 1B. The upper row in Figure 2 features the correlation matrices for all five dynamical regimes (LG1, ON, HG, OFF, LG2), as defined in the caption of Figure 1.


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)

Correlation matrices R (upper row, images A1–A5) and network architectures (lower row, images B1–B5) for all regimes considered in this study.Upper row: correlation matrices for low glucose before stimulation (A1), activation (A2), sustained activity in high glucose (A3), deactivation (A4), and low glucose after stimulation (A5). The color mapping is linear, values of  = 0.0 and  = 1.0 depicted in blue and red, respectively. Lower row: network architectures for low glucose before stimulation (B1), activation (B2), sustained activity in high glucose (B3), deactivation (B4) and low glucose after stimulation (B5). Each red dot represents the physical position of a nucleus of a glucose glucose-responsive cell inside the islet of Langerhans. Dashed lines correspond to cell outlines. Pairs of cells whose correlation exceeds Rth = 0.75 are connected with an arrow. In addition, colors of arrows signify values of Rij: linear coding between 0.75 (yellow) and 1 (dark brown).
© Copyright Policy
Related In: Results  -  Collection

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

pcbi-1002923-g002: Correlation matrices R (upper row, images A1–A5) and network architectures (lower row, images B1–B5) for all regimes considered in this study.Upper row: correlation matrices for low glucose before stimulation (A1), activation (A2), sustained activity in high glucose (A3), deactivation (A4), and low glucose after stimulation (A5). The color mapping is linear, values of  = 0.0 and  = 1.0 depicted in blue and red, respectively. Lower row: network architectures for low glucose before stimulation (B1), activation (B2), sustained activity in high glucose (B3), deactivation (B4) and low glucose after stimulation (B5). Each red dot represents the physical position of a nucleus of a glucose glucose-responsive cell inside the islet of Langerhans. Dashed lines correspond to cell outlines. Pairs of cells whose correlation exceeds Rth = 0.75 are connected with an arrow. In addition, colors of arrows signify values of Rij: linear coding between 0.75 (yellow) and 1 (dark brown).
Mentions: We first calculated the linear correlation coefficient between all pairs of N = 140 cells from a single islet of Langerhans, whose average [Ca2+]i response was shown in Figure 1B. The upper row in Figure 2 features the correlation matrices for all five dynamical regimes (LG1, ON, HG, OFF, LG2), as defined in the caption of Figure 1.

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