Limits...
Modeling of the gap junction of pancreatic β -cells and the robustness of insulin secretion

View Article: PubMed Central - PubMed

ABSTRACT

Pancreatic β-cells are interconnected by gap junctions, which allow small molecules to pass from cell to cell. In spite of the importance of the gap junctions in cellular communication, modeling studies have been limited by the complexity of the system. Here, we propose a mathematical gap junction model that properly takes into account biological functions, and apply this model to the study of the β-cell cluster. We consider both electrical and metabolic features of the system. Then, we find that when a fraction of the ATP-sensitive K+ channels are damaged, robust insulin secretion can only be achieved by gap junctions. Our finding is consistent with recent experiments conducted by Rocheleau et al. Our study also suggests that the free passage of potassium ions through gap junctions plays an important role in achieving metabolic synchronization between β-cells.

No MeSH data available.


A scheme for insulin secretion adopted by Pedersen et al.6 Ge is the extracellular glucose concentration; Gi is the intracellular glucose concentration; G6P is glucose 6-phosphate concentration; FBP is fructose 1-6-bisphosphate concentration; and SERCA means the SERCA pumps.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC5036665&req=5

f2-6_37: A scheme for insulin secretion adopted by Pedersen et al.6 Ge is the extracellular glucose concentration; Gi is the intracellular glucose concentration; G6P is glucose 6-phosphate concentration; FBP is fructose 1-6-bisphosphate concentration; and SERCA means the SERCA pumps.

Mentions: Comparisons among experimental observations have been performed mostly in the context of mathematical models of single β-cells. However, experimental observations are conducted in β-cell clusters, where β-cells are connected with gap junctions. In this letter, we propose a gap junction model that clarifies the relationship between the synchronization phenomena and the cellular processes via gap junctions. From among many proposed single pancreatic β-cell models6,10,12–20, here we adopt one by Pedersen et al.6, and generalize their model from the single-cell level to a multicellular system. The model by Pedersen et al. (see Fig. 2) is not complete as a whole β-cell model, but its relative simplicity facilitates generalization to the multicellular system. We expect that the simplicity of the model can help our intuitive understanding of the numerical investigations. Naturally, this also gives some limitations to our study as discussed in Appendix A.


Modeling of the gap junction of pancreatic β -cells and the robustness of insulin secretion
A scheme for insulin secretion adopted by Pedersen et al.6 Ge is the extracellular glucose concentration; Gi is the intracellular glucose concentration; G6P is glucose 6-phosphate concentration; FBP is fructose 1-6-bisphosphate concentration; and SERCA means the SERCA pumps.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC5036665&req=5

f2-6_37: A scheme for insulin secretion adopted by Pedersen et al.6 Ge is the extracellular glucose concentration; Gi is the intracellular glucose concentration; G6P is glucose 6-phosphate concentration; FBP is fructose 1-6-bisphosphate concentration; and SERCA means the SERCA pumps.
Mentions: Comparisons among experimental observations have been performed mostly in the context of mathematical models of single β-cells. However, experimental observations are conducted in β-cell clusters, where β-cells are connected with gap junctions. In this letter, we propose a gap junction model that clarifies the relationship between the synchronization phenomena and the cellular processes via gap junctions. From among many proposed single pancreatic β-cell models6,10,12–20, here we adopt one by Pedersen et al.6, and generalize their model from the single-cell level to a multicellular system. The model by Pedersen et al. (see Fig. 2) is not complete as a whole β-cell model, but its relative simplicity facilitates generalization to the multicellular system. We expect that the simplicity of the model can help our intuitive understanding of the numerical investigations. Naturally, this also gives some limitations to our study as discussed in Appendix A.

View Article: PubMed Central - PubMed

ABSTRACT

Pancreatic β-cells are interconnected by gap junctions, which allow small molecules to pass from cell to cell. In spite of the importance of the gap junctions in cellular communication, modeling studies have been limited by the complexity of the system. Here, we propose a mathematical gap junction model that properly takes into account biological functions, and apply this model to the study of the β-cell cluster. We consider both electrical and metabolic features of the system. Then, we find that when a fraction of the ATP-sensitive K+ channels are damaged, robust insulin secretion can only be achieved by gap junctions. Our finding is consistent with recent experiments conducted by Rocheleau et al. Our study also suggests that the free passage of potassium ions through gap junctions plays an important role in achieving metabolic synchronization between β-cells.

No MeSH data available.