Electrophysiology of Islet Cells

Drews, Gisela; Koehler, Peter; Düfer, Martina

doi:10.1007/978-94-007-6686-0_5

Cited by 18 publications

(28 citation statements)

References 409 publications

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“…ATP is an important downstream signal of nutrient metabolism, which stimulates insulin release by pancreatic b-cells. The ATP/ADP ratio plays a crucial role in upregulation of GSIS via controlling closure of ATP-sensitive potassium channels (K ATP ), subsequent plasma membrane depolarization, and activation of voltage-gated L-type Ca 2+ channels [2][3][4]. The resulting increase in submembrane Ca 2+ concentration stimulates exocytosis of insulin granules [5].…”

Section: Abstract: Atp Synthase; Diabetes; If1; Ins-1e Cells; Insulinmentioning

confidence: 99%

Regulation of glucose‐stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

et al. 2018

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ATPase Inhibitory factor 1 (IF1) is an endogenous regulator of mitochondrial ATP synthase, which is involved in cellular metabolism. Although great progress has been made, biological roles of IF1 and molecular mechanisms of its action are still to be elucidated. Here, we show that IF1 is present in pancreatic β-cells, bound to the ATP synthase also under normal physiological conditions. IF1 silencing in model pancreatic β-cells (INS-1E) increases insulin secretion over a range of glucose concentrations. The left-shifted dose-response curve reveals excessive insulin secretion even under low glucose, corresponding to fasting conditions. A parallel increase in cellular respiration and ATP levels is observed. To conclude, our results indicate that IF1 is a negative regulator of insulin secretion involved in pancreatic β-cell glucose sensing.

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Section: Abstract: Atp Synthase; Diabetes; If1; Ins-1e Cells; Insulinmentioning

confidence: 99%

Regulation of glucose‐stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

et al. 2018

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“…Insulin secretion from the pancreatic β-cell is driven by increases in the intracellular Ca ] i in the β-cell is determined by the membrane potential, which controls the rate of Ca 2+ influx through voltage-gated Ca 2+ channels [1][2][3]. At low glucose levels, the β-cell membrane is kept hyperpolarized by the activity of adenosine triphosphatesensitive K + channels (K ATP ), and [Ca 2+ ] i is low.…”

Section: Introductionmentioning

confidence: 99%

The Anx7(+/-) Knockout Mutation Alters Electrical and Secretory Responses to Ca²⁺-Mobilizing Agents in Pancreatic �-cells

Mears

Zimliki²,

Atwater³

et al. 2012

Cell Physiol Biochem

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Insulin secretion from the pancreatic β-cell is controlled by changes in membrane potential and intracellular Ca²⁺. The contribution of intracellular Ca²⁺ stores to this process is poorly understood. We have previously shown that β-cells of mice lacking one copy of the Annexin 7 gene (Anx7(+/-)) express reduced levels of IP₃ receptors and defects in IP₃-dependent Ca²⁺ signaling. To further elucidate the effect of the Anx7(+/-) mutation on signaling related to intracellular Ca²⁺ stores in the β-cell, we measured the effects of Ca²⁺ mobilizing agents on electrical activity, intracellular Ca²⁺ and insulin secretion in control and mutant β-cells. We found that the muscarinic agonist carbachol and the ryanodine receptor agonists caffeine and 4-chloro-m-cresol had more potent depolarizing effects on Anx7(+/-) β-cells compared to controls. Accordingly, glucose-induced insulin secretion was augmented to a greater extent by caffeine in mutant islets. Surprisingly, ryanodine receptor-mediated Ca²⁺ mobilization was not affected by the Anx7(+/-) mutation, suggesting that the mechanism underlying the observed differences in electrical and secretory responsiveness does not involve intracellular Ca²⁺ stores. Our results provide evidence that both IP3 receptors and ryanodine receptors play important roles in regulating β-cell membrane potential and insulin secretion, and that the Anx7(+/-) mutation is associated with alterations in the signaling pathways related to these receptors.

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“…K ATP channels of β-cells play an outstanding role in the stimulus-secretion coupling because they sense products of glucose metabolism and convert them into electrical activity that regulates insulin secretion [9]. This 'triggering pathway' of stimulus-secretion coupling comprises glucose metabolism, increase in the ATP/ADP ratio, depolarization of the plasma membrane potential (V m ), increase of the triggering signal, that is, the cytosolic Ca 2+ concentration ([Ca 2+ ] c ), and finally insulin secretion.…”

Section: Physiological Role Of K Atp Channelsmentioning

confidence: 99%

“…In contrast, the 'amplifying pathway' is independent of electrical activity, and augments the sensitivity of the exocytotic machinery to a certain concentration of cytosolic Ca 2+ [10]. During activation of the triggering pathway electrical activity is induced as soon as the threshold potential for the opening of voltage-dependent Ca 2+ (and, depending on the species, Na + channels) is attained [9]. At physiological stimulatory glucose concentrations, the action potentials are grouped in bursts interrupted by silent interburst phases.…”

Section: Physiological Role Of K Atp Channelsmentioning

confidence: 99%

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Role of K_ATP channels in β‐cell resistance to oxidative stress

Drews

Düfer

2012

Diabetes Obesity Metabolism

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The importance of K(ATP) channels in stimulus-secretion coupling of β-cells is well established, although they are not indispensable for the maintenance of glycaemic control. This review article depicts a new role for K(ATP) channels by showing that genetic or pharmacological ablation of these channels protects β-cells against oxidative stress. Increased production of oxidants is a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). T2DM develops when β-cells can no longer compensate for the high demand of insulin resulting from excess fuel intake. Instead β-cells start to secrete less insulin and β-cell mass is diminished by apoptosis. Both, reduction of insulin secretion and β-cell mass induced by oxidative stress, are prevented by deletion or inhibition of K(ATP) channels. These findings may open up new insights into the early treatment of T2DM.

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Electrophysiology of Islet Cells

Cited by 18 publications

References 409 publications

Regulation of glucose‐stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

Regulation of glucose‐stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

The Anx7(+/-) Knockout Mutation Alters Electrical and Secretory Responses to Ca²⁺-Mobilizing Agents in Pancreatic �-cells

Role of K_ATP channels in β‐cell resistance to oxidative stress

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Electrophysiology of Islet Cells

Cited by 18 publications

References 409 publications

Regulation of glucose‐stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

Regulation of glucose‐stimulated insulin secretion by ATPase Inhibitory Factor 1 (IF1)

The Anx7(+/-) Knockout Mutation Alters Electrical and Secretory Responses to Ca2+-Mobilizing Agents in Pancreatic �-cells

Role of KATP channels in β‐cell resistance to oxidative stress

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The Anx7(+/-) Knockout Mutation Alters Electrical and Secretory Responses to Ca²⁺-Mobilizing Agents in Pancreatic �-cells

Role of K_ATP channels in β‐cell resistance to oxidative stress