Study of a glucose-activated anion-selective channel in rat pancreatic β-cells

Best, Leonard

doi:10.1007/s00424-002-0893-y

Cited by 31 publications

(22 citation statements)

References 39 publications

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“…The importance of RVDC for the excitability and secretory response of beta cells is highlighted by the fact that common blockers of RVDC including DIDS, NPPB, 4-hydroxytamoxifen and DCPIB are potent inhibitors of insulin secretion [6,8,12,13,18,[22][23][24]26] and further emphasized by work showing RVDC inhibition and reduction of insulin secretion by certain HIV protease inhibitors [16,37], which could explain the adverse side effects of these antiviral substances on glucose homeostasis.…”

Section: Discussionmentioning

confidence: 99%

“…Of particular interest is the fact that glucose has been found to activate Cl -currents in beta cells (ICl glucose ). Several lines of evidence indicate that the anion channels activated during regulatory volume decrease (RVD) after cell swelling (ICl swell regulatory volume decrease channels/ currents, RVDC) play a pivotal role in the process of insulin secretion: (i) osmotic cell swelling induces Cl -currents in insulin secreting cells (ICl swell ) [5][6][7][8]; (ii) glucose induces cell swelling in pancreatic beta cells [9]; (iii) glucose induces the activation of an anion conductance (ICl glucose ) with features resembling RVDC described in a great variety of cells [10][11][12][13][14][15][16]; (iv) cell swelling per se induces insulin release in clonal beta cells and isolated islets [9,[17][18][19][20][21]; (v) both ICl glucose and the swelling induced insulin release have been shown to be inhibited by the Cl -channel inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), 4-(2-butyl-6,7-dichloro-2-cyclopentyl-indan-1-on-5-yl)oxobutyric acid (DCPIB) and 4-hydroxytamoxifen [12,13,18,[22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

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Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Jakab

Grundbichler

Benický³

et al. 2006

Cell Physiol Biochem

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The metabolic coupling of insulin secretion by pancreatic beta cells is mediated by membrane depolarization due to increased glucose-driven ATP production and closure of K_ATP channels. Alternative pathways may involve the activation of anion channels by cell swelling upon glucose uptake. In INS-1E insulinoma cells superfusion with an isotonic solution containing 20 mM glucose or a 30% hypotonic solution leads to the activation of a chloride conductance with biophysical and pharmacological properties of anion currents activated in many other cell types during regulatory volume decrease (RVD), i.e. outward rectification, inactivation at positive membrane potentials and block by anion channel inhibitors like NPPB, DIDS, 4-hydroxytamoxifen and extracellular ATP. The current is not inhibited by tolbutamide and remains activated for at least 10 min when reducing the extracellular glucose concentration from 20 mM to 5 mM, but inactivates back to control levels when cells are exposed to a 20% hypertonic extracellular solution containing 20 mM glucose. This chloride current can likewise be induced by 20 mM 3-Omethylglucose, which is taken up but not metabolized by the cells, suggesting that cellular sugar uptake is involved in current activation. Fluorescence resonance energy transfer (FRET) experiments show that chloride current activation by 20 mM glucose and glucose-induced cell swelling are accompanied by a significant, transient redistribution of the membrane associated fraction of ICln, a multifunctional ‘connector hub’ protein involved in cell volume regulation and generation of RVD currents.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Jakab

Grundbichler

Benický³

et al. 2006

Cell Physiol Biochem

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“…The Figure 5a shows two typical recordings of an inward channel current that has previously been suggested to be that of the VRAC [11,12]. In the presence of 10 or 5 mmol/l glucose, the application of tolbutamide (20 or 100 µmol/l respectively) further activated the channel current in a reversible manner.…”

Section: Effects Of Tolbutamide On Beta Cell Electrical Activitymentioning

confidence: 85%

“…Activation of this channel by glucose requires metabolism of the sugar [12], so any effect of these drugs on glucose metabolism would also be predicted to influence VRAC activity. Sulphonylureas have been reported to modify glucose metabolism in a number of tissues.…”

Section: Discussionmentioning

confidence: 99%

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Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells

2004

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Aims/hypothesis. Hypoglycaemic sulphonylureas are thought to stimulate insulin release by binding to a sulphonylurea receptor, closing K ATP channels and inducing electrical activity. However, the fact that these drugs stimulate insulin release at high glucose concentrations where K ATP channels are closed suggests additional ionic actions. The aim of this study was to test the hypothesis that sulphonylureas influence the current of the glucose-and volume-regulated anion channel. Methods. Electrical and ion-channel activity were recorded in isolated rat beta cells using the patchclamp technique. 86 Rb + efflux was measured using intact islets. Beta cell volume was measured using a video-imaging technique. Results. In the absence of glucose, tolbutamide (100 µmol/l) transiently depolarised the cells. In the presence of glucose (5 mmol/l), tolbutamide evoked a sustained period of electrical activity, whilst at 10 mmol/l glucose, the drug evoked a pronounced 'silent' depolarisation. In the absence of glucose, tolbutamide inhibited 86 Rb + efflux. However, at 10 mmol/l glucose, tolbutamide induced a transient stimulation of efflux. Tolbutamide potentiated the whole-cell volume-regulated anion conductance in a glucose-dependent manner with an EC 50 of 85 µmol/l. In single channel recordings, tolbutamide increased the channel-open probability. Tolbutamide caused beta cell swelling in the presence of glucose, but not in its absence. Conclusions/interpretation. Tolbutamide can induce beta cell electrical activity by potentiating the glucose-and volume-regulated anion channel current. This effect is probably not due to a direct effect of the drug on the channel, but could be secondary to a metabolic action in the beta cell.

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Electrophysiology of Islet Cells

Drews

Koehler

Düfer

2010

Advances in Experimental Medicine and Biology

129

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Stimulus-Secretion Coupling (SSC) of pancreatic islet cells comprises electrical activity. Changes of the membrane potential (V(m)) are regulated by metabolism-dependent alterations in ion channel activity. This coupling is best explored in beta-cells. The effect of glucose is directly linked to mitochondrial metabolism as the ATP/ADP ratio determines the open probability of ATP-sensitive K(+) channels (K(ATP) channels). Nucleotide sensitivity and concentration in the direct vicinity of the channels are controlled by several factors including phospholipids, fatty acids, and kinases, e.g., creatine and adenylate kinase. Closure of K(ATP) channels leads to depolarization of beta-cells via a yet unknown depolarizing current. Ca(2+) influx during action potentials (APs) results in an increase of the cytosolic Ca(2+) concentration ([Ca(2+)](c)) that triggers exocytosis. APs are elicited by the opening of voltage-dependent Na(+) and/or Ca(2+) channels and repolarized by voltage- and/or Ca(2+)-dependent K(+) channels. At a constant stimulatory glucose concentration APs are clustered in bursts that are interrupted by hyperpolarized interburst phases. Bursting electrical activity induces parallel fluctuations in [Ca(2+)](c) and insulin secretion. Bursts are terminated by I(Kslow) consisting of currents through Ca(2+)-dependent K(+) channels and K(ATP) channels. This review focuses on structure, characteristics, physiological function, and regulation of ion channels in beta-cells. Information about pharmacological drugs acting on K(ATP) channels, K(ATP) channelopathies, and influence of oxidative stress on K(ATP) channel function is provided. One focus is the outstanding significance of L-type Ca(2+) channels for insulin secretion. The role of less well characterized beta-cell channels including voltage-dependent Na(+) channels, volume sensitive anion channels (VSACs), transient receptor potential (TRP)-related channels, and hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is discussed. A model of beta-cell oscillations provides insight in the interplay of the different channels to induce and maintain electrical activity. Regulation of beta-cell electrical activity by hormones and the autonomous nervous system is discussed. alpha- and delta-cells are also equipped with K(ATP) channels, voltage-dependent Na(+), K(+), and Ca(2+) channels. Yet the SSC of these cells is less clear and is not necessarily dependent on K(ATP) channel closure. Different ion channels of alpha- and delta-cells are introduced and SSC in alpha-cells is described in special respect of paracrine effects of insulin and GABA secreted from beta-cells.

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Study of a glucose-activated anion-selective channel in rat pancreatic β-cells

Cited by 31 publications

References 39 publications

Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Glucose Induces Anion Conductance and Cytosol-To-Membrane Transposition of ICln in INS-1E Rat Insulinoma Cells

Tolbutamide potentiates the volume-regulated anion channel current in rat pancreatic beta cells

Electrophysiology of Islet Cells

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