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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.


Essential processes of the insulin secretion6. Glucose is taken into the β-cell by GLUT-2 transporters, and broken down during glycolysis. Glycolytic product pyruvate is taken into the mitochondria in order to produce ATP. The ATP-sensitive K+ channel regulates membrane potential, and Ca2+ flow into the cell, and the insulin release into the blood is prompted by the elevated cytosolic Ca2+ concentration.
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f1-6_37: Essential processes of the insulin secretion6. Glucose is taken into the β-cell by GLUT-2 transporters, and broken down during glycolysis. Glycolytic product pyruvate is taken into the mitochondria in order to produce ATP. The ATP-sensitive K+ channel regulates membrane potential, and Ca2+ flow into the cell, and the insulin release into the blood is prompted by the elevated cytosolic Ca2+ concentration.

Mentions: The essential processes in insulin secretion are as follows (see Fig. 1): ATP-sensitive K+ channels in the plasma membrane are activated by ADP and inactivated by ATP; thus the ratio of these nucleotides determines the fraction of open K(ATP) channels. When the ATP/ADP ratio is elevated, there is a reduction in the number of open K(ATP) channels. This results in membrane depolarization, causing voltage-dependent Ca2+ channels to open. The resulting Ca2+ influx evokes insulin secretion. The difference among various mathematical models may originate in the extent to which common cellular processes beyond the essential processes are taken into account.


Modeling of the gap junction of pancreatic β -cells and the robustness of insulin secretion
Essential processes of the insulin secretion6. Glucose is taken into the β-cell by GLUT-2 transporters, and broken down during glycolysis. Glycolytic product pyruvate is taken into the mitochondria in order to produce ATP. The ATP-sensitive K+ channel regulates membrane potential, and Ca2+ flow into the cell, and the insulin release into the blood is prompted by the elevated cytosolic Ca2+ concentration.
© Copyright Policy
Related In: Results  -  Collection

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

f1-6_37: Essential processes of the insulin secretion6. Glucose is taken into the β-cell by GLUT-2 transporters, and broken down during glycolysis. Glycolytic product pyruvate is taken into the mitochondria in order to produce ATP. The ATP-sensitive K+ channel regulates membrane potential, and Ca2+ flow into the cell, and the insulin release into the blood is prompted by the elevated cytosolic Ca2+ concentration.
Mentions: The essential processes in insulin secretion are as follows (see Fig. 1): ATP-sensitive K+ channels in the plasma membrane are activated by ADP and inactivated by ATP; thus the ratio of these nucleotides determines the fraction of open K(ATP) channels. When the ATP/ADP ratio is elevated, there is a reduction in the number of open K(ATP) channels. This results in membrane depolarization, causing voltage-dependent Ca2+ channels to open. The resulting Ca2+ influx evokes insulin secretion. The difference among various mathematical models may originate in the extent to which common cellular processes beyond the essential processes are taken into account.

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.