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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.


ATP-sensitive K+ current and gap currents, where Ge = 7 mM. Similar to Fig. 8, the blocked or damaged cell significantly increases the outward gap currents IG(K) and IG(Ca) from the cell. (a) IK(ATP) of the case of Fig. 4(a), (b)IK(ATP) of the case of Fig. 9(e), (c) gap currents IG(K) and IG(Ca) of the cases of Figs. 4(a) and 9(e). (d) a comparison of  and . They are nearly identical and in the same range of value of IK(ATP) in equilibrium state (2000 fA∼10000 fA) in Fig. 9(a).
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f9-6_37: ATP-sensitive K+ current and gap currents, where Ge = 7 mM. Similar to Fig. 8, the blocked or damaged cell significantly increases the outward gap currents IG(K) and IG(Ca) from the cell. (a) IK(ATP) of the case of Fig. 4(a), (b)IK(ATP) of the case of Fig. 9(e), (c) gap currents IG(K) and IG(Ca) of the cases of Figs. 4(a) and 9(e). (d) a comparison of and . They are nearly identical and in the same range of value of IK(ATP) in equilibrium state (2000 fA∼10000 fA) in Fig. 9(a).

Mentions: For the further confirmation of the above analysis, we have increased the extracellular glucose concentration Ge from 2 mM to 7 mM as shown in Fig. 9. Since we have already studied the case where both cells are normal as presented in Fig. 4(a), only the blocked case is shown in Fig. 9(e) except gap currents and IK(ATP).When Ge= 7 mM, the insulin is constantly secreted, but the role of gap junction for the metabolic synchronization is still important when some cell is damaged.


Modeling of the gap junction of pancreatic β -cells and the robustness of insulin secretion
ATP-sensitive K+ current and gap currents, where Ge = 7 mM. Similar to Fig. 8, the blocked or damaged cell significantly increases the outward gap currents IG(K) and IG(Ca) from the cell. (a) IK(ATP) of the case of Fig. 4(a), (b)IK(ATP) of the case of Fig. 9(e), (c) gap currents IG(K) and IG(Ca) of the cases of Figs. 4(a) and 9(e). (d) a comparison of  and . They are nearly identical and in the same range of value of IK(ATP) in equilibrium state (2000 fA∼10000 fA) in Fig. 9(a).
© Copyright Policy
Related In: Results  -  Collection

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

f9-6_37: ATP-sensitive K+ current and gap currents, where Ge = 7 mM. Similar to Fig. 8, the blocked or damaged cell significantly increases the outward gap currents IG(K) and IG(Ca) from the cell. (a) IK(ATP) of the case of Fig. 4(a), (b)IK(ATP) of the case of Fig. 9(e), (c) gap currents IG(K) and IG(Ca) of the cases of Figs. 4(a) and 9(e). (d) a comparison of and . They are nearly identical and in the same range of value of IK(ATP) in equilibrium state (2000 fA∼10000 fA) in Fig. 9(a).
Mentions: For the further confirmation of the above analysis, we have increased the extracellular glucose concentration Ge from 2 mM to 7 mM as shown in Fig. 9. Since we have already studied the case where both cells are normal as presented in Fig. 4(a), only the blocked case is shown in Fig. 9(e) except gap currents and IK(ATP).When Ge= 7 mM, the insulin is constantly secreted, but the role of gap junction for the metabolic synchronization is still important when some cell is damaged.

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.