Voltage-Gated Ion Channels in Human Pancreatic β-Cells: Electrophysiological Characterization and Role in Insulin Secretion
Abstract
Objective To characterize the voltage-gated ion channels in human beta-cells from nondiabetic donors and their role in glucose-stimulated insulin release. Research design and methods Insulin release was measured from intact islets. Whole-cell patch-clamp experiments and measurements of cell capacitance were performed on isolated beta-cells. The ion channel complement was determined by quantitative PCR. Results Human beta-cells express two types of voltage-gated K(+) currents that flow through delayed rectifying (K(V)2.1/2.2) and large-conductance Ca(2+)-activated K(+) (BK) channels. Blockade of BK channels (using iberiotoxin) increased action potential amplitude and enhanced insulin secretion by 70%, whereas inhibition of K(V)2.1/2.2 (with stromatoxin) was without stimulatory effect on electrical activity and secretion. Voltage-gated tetrodotoxin (TTX)-sensitive Na(+) currents (Na(V)1.6/1.7) contribute to the upstroke of action potentials. Inhibition of Na(+) currents with TTX reduced glucose-stimulated (6-20 mmol/l) insulin secretion by 55-70%. Human beta-cells are equipped with L- (Ca(V)1.3), P/Q- (Ca(V)2.1), and T- (Ca(V)3.2), but not N- or R-type Ca(2+) channels. Blockade of L-type channels abolished glucose-stimulated insulin release, while inhibition of T- and P/Q-type Ca(2+) channels reduced glucose-induced (6 mmol/l) secretion by 60-70%. Membrane potential recordings suggest that L- and T-type Ca(2+) channels participate in action potential generation. Blockade of P/Q…
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Activation of TTX-sensitive Na+ channels plays a prominent role in human β-cell action potential firing at low glucose but not at high glucose.
“For example, activation of TTX-sensitive Na+ channels plays a prominent role in human β-cell action potential firing at low glucose but not at high glucose (90, 521) - and in most mouse β-cells it is not involved in action potential firing at all (761).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
Stromatoxin has little effect on action potential height in human β-cells.
“This explains why stromatoxin has little effect on action potential height in human β-cells.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
In human β-cells, L-type and P/Q-type Ca2+ channels contribute 50% and 25%, respectively, of the peak current at 0 mV, with the rest principally attributable to T-type Ca2+ channels.
“L-type and P/Q-type Ca2+ channels contribute 50% and 25%, respectively, of the peak current at 0 mV, with the rest being principally attributable to T-type Ca2+ channels (90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
T-type Ca2+ channels in human β-cells give a transient current detectable at -60 mV, maximal at -40 to -30 mV with peak amplitude ≈4 pA/pF, and are reversibly blocked by NNC 55-3096.
“It gives rise to a transient (rapidly inactivating) current that in human β-cells can be detected at membrane potentials as negative as -60 mV. The whole-cell current is maximal at -40 to -30 mV, where its peak amplitude is ≈4 pA/pF, and it is reversibly blocked by the selective T-type Ca2+ channel blocker NNC 55-3096 (90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
The time constant of activation of the human β-cell delayed rectifier at -20 mV is greater than 10 ms.
“The time constant of activation (τm) measured at -20 mV is >10 ms.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
TTX reduces insulin secretion in human β-cells, with its effect particularly strong at 6 mM glucose and weaker at 10-20 mM glucose.
“Furthermore, TTX reduces insulin secretion: its effect is particularly strong at glucose concentrations just above the threshold for GIIS (6 mM) but is weaker at higher (10-20 mM) concentrations (52, 90) (see Figure 13C-D).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
Human β-cells possess a slowly activating, stromatoxin-sensitive delayed-rectifier K+ current.
“Human β-cells possess a slowly activating, stromatoxin-sensitive (delayed-rectifier) K+ current (90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
Inhibition of BK channels with iberiotoxin is associated with an approximately 10 mV increase in action potential amplitude and stimulation of insulin secretion in human β-cells.
“As predicted, inhibition of BK channels with iberiotoxin was associated with an ~10 mV increase in action potential amplitude and stimulation of insulin secretion (90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
Human β-cells (unlike mouse β-cells) are equipped with T-type Ca2+-channels that activate at membrane potentials as negative as -60 mV.
“Second, human β-cells (unlike mouse β-cells) are equipped with T-type Ca2+-channels that activate at membrane potentials as negative as -60 mV (52, 90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
At the peak of the action potential (-20 mV and above), P/Q-type Ca2+ channels open and trigger exocytosis of insulin granules.
“At the peak of the action potential (-20 mV and above), P/Q-type Ca2+ channels open and trigger exocytosis of insulin granules (51, 90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
Na+ channels play a particularly important role at glucose concentrations just above the threshold for triggering electrical activity in human β-cells.
“Na+ channels play a particularly important role at glucose concentrations just above the threshold for triggering electrical activity (52, 90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
The elevation of [Ca2+]i resulting from opening of Ca2+ channels leads to activation of BK channels and initiates action potential repolarization.
“The elevation of [Ca2+]i resulting from the opening of the Ca2+ channels leads to activation of BK channels and initiates action potential repolarization (51, 90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
Low-amplitude action potentials generated at high glucose (once Na+ channel inactivation has occurred) will principally be associated with Ca2+ entry via L-type Ca2+ channels.
“Accordingly, the low-amplitude action potentials generated at high glucose (once Na+ channel inactivation has occurred) will principally be associated with Ca2+ entry via L-type Ca2+ channels as these activate at more negative voltages than the P/Q-type Ca2+ channels (90).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
The kinetics of 'asynchronous' exocytosis in human β-cells largely mirrors the depolarization-evoked [Ca2+]i transients.
“The kinetics of ‘asynchronous’ exocytosis in human β-cells largely mirrors the depolarization-evoked [Ca2+]i transients (Figure 21B).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
In isolated human β-cells, exocytosis proceeds beyond the end of the depolarization and exocytotic responses elicited by short depolarizations are much smaller than in mouse β-cells.
“In isolated human β-cells, exocytosis proceeds beyond the end of the depolarization (90, 91) (Figure 21B) and exocytotic responses elicited by short depolarizations are much smaller than in mouse β-cells (Figure 21A).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [90]
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“6; expressed in human islets [32] oltage-gated Ca channel present in human pancreatic b-cells; role in insulin n [32] oltage-gated Ca channel present in human pancreatic b-cells; role in insulin n [35] receptor, alpha 4 subunit; low levels found in human islets [33] receptor, alpha 5 subunit; non-detected in human isl…”
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“are, as in human beta cells [13], indispensable for action potential generation (Fig.”
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“The expression of many of the voltage dependent Ca2+ channels present in human b cells (Braun et al., 2008) was markedly reduced: Ca2+-channel genes affected include the P/Q-type Ca2+ channels (CACNA1A; FC, 2.39; p = 0.006), L-type Ca2+ channels (CACNA1C; FC, 1.48; p = 6.4 3 10 5 and CACNA1D; FC,…”
BackgroundInfluentialSelf-citationZhang, Q., Chibalina, M. V., Bengtsson, M., Groschner, L. N., Ramracheya, R., Rorsman, N. J. G., Leiss, V., Nassar, M. A., Welling, A., Gribble, F. M., et al. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.274209 · Cited by 90 · see citing works
“Its smallness probably explains why it escaped detection in the earlier study (Braun et al. 2008).”
BackgroundResultInfluentialSelf-citationPancreatic Beta-cell Dysfunction in Type 2 Diabetes
Khin, P. P., Lee, J. H., & Jun, H. (2023) · European Journal of Inflammation · doi:10.1177/1721727x231154152 · Cited by 127 · see citing works
“24,25 Delayed recti fi er potassium (K D ) channels are the main component of the K+ channel and control resting potential and AP repolarization in many cell types.”
BackgroundArnoux, J., de Lonlay, P., Ribeiro, M., Hussain, K., Blankenstein, O., Mohnike, K., Valayannopoulos, V., Robert, J.-J., Rahier, J., Sempoux, C., et al. (2020) · Contemporary endocrinology · doi:10.1007/978-3-030-02961-6 · Cited by 88
“SCHAD-HI cases have presented with both fasting and protein-induced hyperinsulinemic hypoglycemia, ranging from the early neonatal period to 14 months [58].”
Eliasson, L. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.02.043 · Cited by 88 · see citing works
A voltage-dependent K+ channel in the lysosome is required for refilling lysosomal Ca2+ stores
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“In INS-1 cells, which express β3 subunits (Braun et al., 2008; Torres et al., 2014), and cultured BECs, LysoKVCa exhibited voltage-dependent inactivation or blockage at high voltages (Fig.”
BackgroundShortcomings of current models of glucose‐induced insulin secretion
Henquin, J., Nenquin, M., Ravier, M., & Szollosi, A. (2009) · Diabetes, obesity and metabolism · doi:10.1111/j.1463-1326.2009.01109.x · Cited by 88
Ionic mechanisms in pancreatic β cell signaling
Yang, S. N., Shi, Y., Yang, G., Li, Y., Yu, J. H., & Berggren, P. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1680-6 · Cited by 91 · see citing works
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Gs/Gq signaling switch in β cells defines incretin effectiveness in diabetes.
Oduori, O. S., Murao, N., Shimomura, K., Takahashi, H., Zhang, Q., Dou, H.-Q., Sakai, S., Minami, K., Chanclón, B., Guida, C., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci140046 · Cited by 85 · see citing works
Self-citationChannel regulation of glucose sensing in the pancreatic beta-cell.
Hiriart, M., & Aguilar-Bryan, L. (2008) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.90493.2008 · Cited by 85 · see citing works
“Na channels are present and participate in GSIS by depolarizing the membrane in canine and human beta-cells (68, 8, 11).”
InfluentialKv5, Kv6, Kv8, and Kv9 subunits: No simple silent bystanders
Bocksteins, E. (2016) · The Journal of General Physiology · doi:10.1085/jgp.201511507 · Cited by 84 · see citing works
Reinbothe, T. M., Alkayyali, S., Ahlqvist, E., Tuomi, T., Isomaa, B., Lyssenko, V., & Renström, E. (2013) · Diabetologia · doi:10.1007/s00125-012-2758-z · Cited by 84 · see citing works
“After 48 h, cells were used for electrophysiological capacity measurements as previously described [15].”
BackgroundMethodResultInfluentialZhu, L., Almaça, J., Dadi, P., Hong, H., Sakamoto, W., Rossi, M., Lee, R. J., Vierra, N., Lu, H.-Y., Cui, Y.-H., et al. (2017) · Nature Communications · doi:10.1038/ncomms14295 · Cited by 82 · see citing works
Rorsman, P., Ramracheya, R. D., Rorsman, N. J. G., & Zhang, Q. (2014) · Diabetologia · doi:10.1007/s00125-014-3279-8 · Cited by 89 · see citing works
“Electrophysiologically, human alpha cells are almost identical to human beta cells [51, 52].”
BackgroundSelf-citationStützer, I., Selevsek, N., Esterházy, D., Schmidt, A., Aebersold, R., & Stoffel, M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444703 · Cited by 82 · see citing works
Yan-Do, R., Duong, E., Manning Fox, J. E., Dai, X., Suzuki, K., Khan, S., Bautista, A., Ferdaoussi, M., Lyon, J., Wu, X., et al. (2016) · Diabetes · doi:10.2337/db15-1272 · Cited by 82 · see citing works
“After experiments, the cell types were established by immunocytochemistry, as previously described (25).”
MethodResultSelf-citationFriend and foe: β-cell Ca2+ signaling and the development of diabetes
Sabatini, P. V., Speckmann, T., & Lynn, F. C. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.12.007 · Cited by 97 · see citing works
“In human b-cells, L-VGCCs are activated at a membrane potential of 40 mV and, in concert with T-type and P/Q-type Ca2þ channels, allow Ca2þ influx to elicit insulin exocytosis [6].”
BackgroundYashiro, H., Tsujihata, Y., Takeuchi, K., Hazama, M., Johnson, P. R. V., & Rorsman, P. (2012) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.187708 · Cited by 84 · see citing works
Self-citationChepurny, O., Kelley, G., Dzhura, I., Leech, C. A., Roe, M., Dzhura, E., Li, X., Schwede, F., Genieser, H., & Holz, G. G. (2010) · American Journal of Physiology. Endocrinology and Metabolism · doi:10.1152/ajpendo.00630.2009 · Cited by 80 · see citing works
“This RRP undergoes exocytosis in response to high concentrations (10–20 M) of Ca(2) that exist in microdomains and which form at the inner mouths of VDCCs that open in response to depolarization (4, 6).”
BackgroundCa2+ channel clustering with insulin-containing granules is disturbed in type 2 diabetes
Gandasi, N. R., Yin, P., Riz, M., Chibalina, M. V., Cortese, G., Lund, P.-E., Matveev, V., Rorsman, P., Sherman, A., Pedersen, M. G., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88491 · Cited by 90 · see citing works
Self-citationIon channels and regulation of insulin secretion in human β-cells: a computational systems analysis
Fridlyand, L. E., Jacobson, D. A., & Philipson, L. H. (2013) · Islets · doi:10.4161/isl.24166 · Cited by 78 · see citing works
“, during a large Ca influx a cell quickly increases Ca concentration in microdomains.(10,12) We therefore included in our model an increased sensitivity of BK channel currents to changes of [Ca] c than for isolated BK channels to simulate the effect of microdomain Ca (Eqs.”
BackgroundMethodInfluentialDahal, G. R., Pradhan, S., & Bates, E. (2017) · Development · doi:10.1242/dev.146647 · Cited by 76 · see citing works
“Inhibition of Kir channels depolarizes cells, increases intracellular calcium and increases the secretion from excitable cells (Bondy et al., 1987; Braun et al., 2008; Cilz et al., 2014; Misler et al., 1992; Riz et al., 2015; Rorsman and Braun, 2013), and we hypothesize that a similar mechanism could be at play in the…”
BackgroundInfluentialMathematical Modeling of Heterogeneous Electrophysiological Responses in Human β-Cells
Riz, M., Braun, M., & Pedersen, M. G. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003389 · Cited by 73 · see citing works
“, with respect to their palette of expressed Ca -channels and the role of Na -channels, which contribute to electrical activity in human but not in rodent b-cells [1,3].”
BackgroundMethodInfluentialSelf-citationJacobson, D. A., Mendez, F., Thompson, M., Torres, J., Cochet, O., & Philipson, L. H. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.190207 · Cited by 73 · see citing works
“1−/− islets may also help to understand this aspect of human islet function (Braun et al. 2008).”
BackgroundInfluentialLi, X., Herrington, J., Petrov, A., Ge, L., Eiermann, G., Xiong, Y., Jensen, M., Hohmeier, H., Newgard, C., Garcia, M., et al. (2013) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.112.199083 · Cited by 72 · see citing works
“…glucose levels in vivo (Jacobson et al., 2007), pharmacologic studies with Kv2 inhibitors have not convincingly shown a role for Kv2 channels in regulating glucose stimulated insulin secretion (GSIS) in islets (Herrington et al., 2006; Braun et al., 2008), and, moreover the biologic role(s) of Kv2.”
BackgroundHeterogenous impairment of α-cell function in type 2 diabetes is linked to cell maturation state
Dai, X.-Q., Camunas-Soler, J., Briant, L., dos Santos, T., Spigelman, A., Walker, E., Drigo, R. A., Bautista, A., Jones, R. C., Avrahami, D., et al. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2021.12.021 · Cited by 69 · see citing works
“Unlike in mice, but similar to previous reports (Braun et al., 2008; Ramracheya et al., 2010), Na channel properties are similar between human a and b cells and could not be reliably used alone to distinguish these cell types (Figures 5B, 5C, and S4C).”
ResultSelf-citationde Marchi, U., Thévenet, J., Hermant, A., Dioum, E., & Wiederkehr, A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.513184 · Cited by 68 · see citing works
“and NNC 55-0396, which were shown previously to almost completely prevent voltage-dependent Ca(2) uptake in human beta cells (34).”
BackgroundMethodMinireview: intraislet regulation of insulin secretion in humans.
Rutter, G., & Hodson, D. (2013) · Molecular Endocrinology · doi:10.1210/me.2013-1278 · Cited by 68 · see citing works
The Human Islet: Mini-organ with Mega-impact.
Walker, J. T., Saunders, D. C., Brissova, M., & Powers, A. (2021) · Endocrine reviews · doi:10.1210/endrev/bnab010 · Cited by 67 · see citing works
Voltage gated sodium channels in cancer and their potential mechanisms of action
Angus, M., & Ruben, P. (2019) · Channels · doi:10.1080/19336950.2019.1666455 · Cited by 66 · see citing works
“[28] Braun M, Ramracheya R, Bengtsson M, et al.”
BackgroundCalcium Signaling in the Islets
Islam, M. S. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-90-481-3271-3_11 · Cited by 63 · see citing works
“In contrast, their roles in mediating exocytosis are less pronounced [69].”
BackgroundInfluentialCha, C. Y., Nakamura, Y., Himeno, Y., Wang, J., Fujimoto, S., Inagaki, N., Earm, Y. E., & Noma, A. (2011) · The Journal of General Physiology · doi:10.1085/jgp.201110611 · Cited by 61 · see citing works
“Similar transient outward currents coupled with ICaV have also been reported in human cells (Herrington et al., 2005; Braun et al., 2008).”
BackgroundMethodInfluentialThe Large-Conductance, Calcium-Activated Potassium Channel: A Big Key Regulator of Cell Physiology
Sancho, M., & Kyle, B. D. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.750615 · Cited by 64
A Biophysical Model of Electrical Activity in Human β-Cells
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“050 nS/pF (3) thCaT 7 ms (3) VmCaT 40 mV (3) nmCaT 4 mV (3) VhCaT 64 mV (3) nhCaT 8 mV (3) gCaPQ 0.”
BackgroundInfluentialThe role of GABA in islet function
Hagan, D., Ferreira, S. M., Santos, G., & Phelps, E. A. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.972115 · Cited by 62 · see citing works
Maleńczyk, K., Girach, F., Szodorai, E., Storm, P., Segerstolpe, Å., Tortoriello, G., Schnell, R., Mulder, J., Romanov, R., Borók, E., et al. (2017) · EMBO Journal · doi:10.15252/embj.201695347 · Cited by 60 · see citing works
“Glucose metabolism-dependent activity of voltage-gated L-, P/Q-and T-type Ca 2+ channels is considered the primary factor affecting Ca 2+ homoeostasis in pancreatic b -cells (Braun et al , 2008).”
GPR55‐dependent stimulation of insulin secretion from isolated mouse and human islets of Langerhans
Liu, B., Song, S., Ruz-Maldonado, I., Pingitore, A., Huang, G. C., Baker, D., Jones, P. M., & Persaud, S. (2016) · Diabetes, obesity and metabolism · doi:10.1111/dom.12780 · Cited by 60 · see citing works
Exocytotic Properties of Human Pancreatic β‐cells
Braun, M., Ramracheya, R., Johnson, P. R., & Rorsman, P. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2008.03992.x · Cited by 60 · see citing works
Self-citationFunctional identification of islet cell types by electrophysiological fingerprinting
Briant, L. J. B., Zhang, Q., Vergari, E., Kellard, J. A., Rodriguez, B., Ashcroft, F. M., & Rorsman, P. (2017) · Journal of The Royal Society Interface · doi:10.1098/rsif.2016.0999 · Cited by 59 · see citing works
Self-citationDadi, P., Vierra, N., Ustione, A., Piston, D., Colbran, R., & Jacobson, D. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.562587 · Cited by 59 · see citing works
“Glucose-stimulated activation of LTCCs is responsible for the upstroke of the action potential (AP), resulting in -cell firing (30, 31).”
BackgroundTransient Receptor Potential Cation Channels in Pancreatic β Cells
Colsoul, B., Vennekens, R., & Nilius, B. (2011) · Reviews of physiology, biochemistry and pharmacology · doi:10.1007/112_2011_2 · Cited by 65 · see citing works
Houamed, K. M., Sweet, I. R., & Satin, L. S. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2009.184341 · Cited by 59 · see citing works
The Role of cAMP in Beta Cell Stimulus–Secretion and Intercellular Coupling
Stožer, A., Leitgeb, E. P., Pohorec, V., Dolenšek, J., Bombek, L. K., Gosak, M., & Klemen, M. S. (2021) · Cells · doi:10.3390/cells10071658 · Cited by 64 · see citing works
“Kv channels In human beta cells, the voltage-dependent K+ current is mediated by delayed rectifying K+ (Kv) channels and big K+ conductance (BK) channels [43] which are involved in the repolarization phase of action potentials [44].”
BackgroundThe Evolutionary Assembly of Neuronal Machinery
Arendt, D. (2020) · Current Biology · doi:10.1016/j.cub.2020.04.008 · Cited by 67 · see citing works
LRRK2 Regulates Voltage-Gated Calcium Channel Function
Bedford, C., Sears, C., Pérez-Carrión, M., Piccoli, G., & Condliffe, S. B. (2016) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2016.00035 · Cited by 57 · see citing works
“1 channels provide a rapid, localized increase in intracellular Ca2+ that stimulates vesicle fusion, driving the physiological processes of neurotransmission (Qian andNoebels, 2001) and hormone release (Braun et al., 2008).”
BackgroundMarchand, S. L., & Piston, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047084 · Cited by 57 · see citing works
“L-type calcium channels start to open at membrane potential higher than 250 mV and are maximally activated between 220 mV and +10 mV [31].”
BackgroundIon Channels of the Islets in Type 2 Diabetes
Jacobson, D. A., & Shyng, S. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.08.014 · Cited by 56 · see citing works
Beta-cell hubs maintain Ca2+ oscillations in human and mouse islet simulations
Lei, C. L., Kellard, J. A., Hara, M., Johnson, J. D., Rodríguez, B., & Briant, L. (2018) · Islets · doi:10.1080/19382014.2018.1493316 · Cited by 56 · see citing works
“Furthermore, the data that these models are based on uses recordings from dispersed human β-cells that were cultured in media without the addition of any serum.(50,73,74) It has subsequently been shown that supplementation of islets with serum is essential for preserving islet function.”
BackgroundSynaptotagmin-7 Functions to Replenish Insulin Granules for Exocytosis in Human Islet β-Cells
Dolai, S., Xie, L., Zhu, D., Liang, T., Qin, T., Xie, H., Kang, Y., Chapman, E. R., & Gaisano, H. Y. (2016) · Diabetes · doi:10.2337/db15-1436 · Cited by 55 · see citing works
“Boxed areas are shown enlarged (34) at the bottom to more clearly show that Syt-7 is present not only in insulin SGs (yellow in merge image) but also in cytoplasmic areas outside insulin SGs (green in merge image, arrowheads).”
Background
- Authors
- Braun, M., Ramracheya, R., Bengtsson, M., Zhang, Q., Karanauskaite, J., Partridge, C., Johnson, P. R., & Rorsman, P.
- Affiliations
- Churchill Hospital (GB)
- John Radcliffe Hospital (GB)
- Corresponding author
- Braun, Matthias
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2008-06-01
- Volume
- 57
- Issue
- 6
- Pages
- 1618-1628
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2110906674
- Cited by
- 417
- References
- 0
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 21 · 2023: 22 · 2022: 21 · 2021: 30 · 2020: 20 · 2019: 21 · 2018: 22 · 2017: 34 · 2016: 22 · 2015: 29 · 2014: 34 · 2013: 19 · 2012: 29
- FWCI
- 25.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institute for Health and Care Research
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- voltage-gated ion channels, pancreatic beta cells, insulin secretion, glucose-stimulated insulin secretion, BK channels, L-type calcium channels, P/Q-type calcium channels, T-type calcium channels, action potential, membrane repolarization, exocytosis, iberiotoxin
- MeSH terms
- Insulin Secretion, Cells, Cultured, Cobalt, Electrophysiology, Humans, Insulin, Islets of Langerhans, Peptides, Scorpion Venoms, Reverse Transcriptase Polymerase Chain Reaction, omega-Conotoxin GVIA, omega-Agatoxin IVA, Gene Expression Profiling, Insulin-Secreting Cells, Large-Conductance Calcium-Activated Potassium Channels
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