Limits...
Investigating the role of islet cytoarchitecture in its oscillation using a new beta-cell cluster model.

Nittala A, Ghosh S, Wang X - PLoS ONE (2007)

Bottom Line: In addition, normal beta-cell clusters are robust against significant perturbation to their architecture, including the presence of non-beta cells or dead beta cells.Our results suggest that the bursting characteristics of a beta-cell cluster depend quantitatively on its architecture in a non-linear fashion.These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.

ABSTRACT
The oscillatory insulin release is fundamental to normal glycemic control. The basis of the oscillation is the intercellular coupling and bursting synchronization of beta cells in each islet. The functional role of islet beta cell mass organization with respect to its oscillatory bursting is not well understood. This is of special interest in view of the recent finding of islet cytoarchitectural differences between human and animal models. In this study we developed a new hexagonal closest packing (HCP) cell cluster model. The model captures more accurately the real islet cell organization than the simple cubic packing (SCP) cluster that is conventionally used. Using our new model we investigated the functional characteristics of beta-cell clusters, including the fraction of cells able to burst f(b), the synchronization index lambda of the bursting beta cells, the bursting period T(b), the plateau fraction p(f), and the amplitude of intracellular calcium oscillation [Ca]. We determined their dependence on cluster architectural parameters including number of cells n(beta), number of inter-beta cell couplings of each beta cell n(c), and the coupling strength g(c). We found that at low values of n(beta), n(c) and g(c), the oscillation regularity improves with their increasing values. This functional gain plateaus around their physiological values in real islets, at n(beta) approximately 100, n(c) approximately 6 and g(c) approximately 200 pS. In addition, normal beta-cell clusters are robust against significant perturbation to their architecture, including the presence of non-beta cells or dead beta cells. In clusters with n(beta)> approximately 100, coordinated beta-cell bursting can be maintained at up to 70% of beta-cell loss, which is consistent with laboratory and clinical findings of islets. Our results suggest that the bursting characteristics of a beta-cell cluster depend quantitatively on its architecture in a non-linear fashion. These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions.

Show MeSH

Related in: MedlinePlus

The fraction of β cells able to burst fb, and their synchronization λ, are less influenced by cluster size nβ in HCP clusters.Plotted are mean and standard deviation of the corresponding 10 replicate clusters at each condition.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC1991600&req=5

pone-0000983-g002: The fraction of β cells able to burst fb, and their synchronization λ, are less influenced by cluster size nβ in HCP clusters.Plotted are mean and standard deviation of the corresponding 10 replicate clusters at each condition.

Mentions: We first compared the fraction of burster cells fb and their synchronization index λ for all SCP (SCP-8, -27, -64, -125, -216, and -343) and HCP (HCP-13, -57, -153 and -323) clusters we have simulated, at different gap junctional coupling strength from gc = 25 pS to gc = 1000 pS. We find that at or above normal physiological conditions of gc∼150–250 pS [14], [40], [41], the SCP and HCP clusters did not differ much and all cluster sizes exhibited a high fraction (>99%) of well synchronized burster cells (λ>0.95). Figure 2 presents the results at gc = 200 pS. It is known that under pathological conditions, the intercellular coupling can be significantly impaired. For example, chronic hyperglycemia can reduce the gap junctional conductance between cells [42]–[45]. A particular case, when gc reduces to 50 pS, is also plotted in figure 2 for both cluster types. Over 99% of the β cells in HCP clusters are still able to burst, while this number dropped significantly in the SCP clusters with the smaller ones affected the most. Additionally, the synchronization among the burster cells is also significantly less in the SCP clusters, especially the smaller SCP clusters.


Investigating the role of islet cytoarchitecture in its oscillation using a new beta-cell cluster model.

Nittala A, Ghosh S, Wang X - PLoS ONE (2007)

The fraction of β cells able to burst fb, and their synchronization λ, are less influenced by cluster size nβ in HCP clusters.Plotted are mean and standard deviation of the corresponding 10 replicate clusters at each condition.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1991600&req=5

pone-0000983-g002: The fraction of β cells able to burst fb, and their synchronization λ, are less influenced by cluster size nβ in HCP clusters.Plotted are mean and standard deviation of the corresponding 10 replicate clusters at each condition.
Mentions: We first compared the fraction of burster cells fb and their synchronization index λ for all SCP (SCP-8, -27, -64, -125, -216, and -343) and HCP (HCP-13, -57, -153 and -323) clusters we have simulated, at different gap junctional coupling strength from gc = 25 pS to gc = 1000 pS. We find that at or above normal physiological conditions of gc∼150–250 pS [14], [40], [41], the SCP and HCP clusters did not differ much and all cluster sizes exhibited a high fraction (>99%) of well synchronized burster cells (λ>0.95). Figure 2 presents the results at gc = 200 pS. It is known that under pathological conditions, the intercellular coupling can be significantly impaired. For example, chronic hyperglycemia can reduce the gap junctional conductance between cells [42]–[45]. A particular case, when gc reduces to 50 pS, is also plotted in figure 2 for both cluster types. Over 99% of the β cells in HCP clusters are still able to burst, while this number dropped significantly in the SCP clusters with the smaller ones affected the most. Additionally, the synchronization among the burster cells is also significantly less in the SCP clusters, especially the smaller SCP clusters.

Bottom Line: In addition, normal beta-cell clusters are robust against significant perturbation to their architecture, including the presence of non-beta cells or dead beta cells.Our results suggest that the bursting characteristics of a beta-cell cluster depend quantitatively on its architecture in a non-linear fashion.These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions.

View Article: PubMed Central - PubMed

Affiliation: Max McGee National Research Center for Juvenile Diabetes, Medical College of Wisconsin, Milwaukee, Wisconsin, United States of America.

ABSTRACT
The oscillatory insulin release is fundamental to normal glycemic control. The basis of the oscillation is the intercellular coupling and bursting synchronization of beta cells in each islet. The functional role of islet beta cell mass organization with respect to its oscillatory bursting is not well understood. This is of special interest in view of the recent finding of islet cytoarchitectural differences between human and animal models. In this study we developed a new hexagonal closest packing (HCP) cell cluster model. The model captures more accurately the real islet cell organization than the simple cubic packing (SCP) cluster that is conventionally used. Using our new model we investigated the functional characteristics of beta-cell clusters, including the fraction of cells able to burst f(b), the synchronization index lambda of the bursting beta cells, the bursting period T(b), the plateau fraction p(f), and the amplitude of intracellular calcium oscillation [Ca]. We determined their dependence on cluster architectural parameters including number of cells n(beta), number of inter-beta cell couplings of each beta cell n(c), and the coupling strength g(c). We found that at low values of n(beta), n(c) and g(c), the oscillation regularity improves with their increasing values. This functional gain plateaus around their physiological values in real islets, at n(beta) approximately 100, n(c) approximately 6 and g(c) approximately 200 pS. In addition, normal beta-cell clusters are robust against significant perturbation to their architecture, including the presence of non-beta cells or dead beta cells. In clusters with n(beta)> approximately 100, coordinated beta-cell bursting can be maintained at up to 70% of beta-cell loss, which is consistent with laboratory and clinical findings of islets. Our results suggest that the bursting characteristics of a beta-cell cluster depend quantitatively on its architecture in a non-linear fashion. These findings are important to understand the islet bursting phenomenon and the regulation of insulin secretion, under both physiological and pathological conditions.

Show MeSH
Related in: MedlinePlus