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A Subset of 50 Secretory Granules in Close Contact With l-Type Ca2+ Channels Accounts for First-Phase Insulin Secretion in Mouse β-Cells
Abstract
Capacitance measurements were applied to mouse pancreatic beta-cells to elucidate the cellular mechanisms underlying biphasic insulin secretion. We report here that only 10,000 granules are immediately available for release. The releasable granules tightly associate with the voltage-gated alpha(1C) Ca(2+) channels, and it is proposed that the release of these granules accounts for first-phase insulin secretion. Subsequent replenishment of the releasable pool by priming of previously nonreleasable granules is required for second-phase insulin secretion. The latter reaction depends on intragranular acidification due to the concerted action of granular bafilomycin-sensitive v-type H(+)-ATPase and 4,4-diisothiocyanostilbene-2,2-disulfonate--blockable ClC-3 Cl(-) channels. Lowering the cytoplasmic ATP/ADP ratio prevents granule acidification, granule priming, and refilling of the releasable pool. The latter finding provides an explanation to the transient nature of insulin secretion elicited by, for example, high extracellular K(+) in the absence of metabolizable fuels.
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“At ADP concentrations >1 mM, depolarization-evoked exocytosis in the presence of 3 mM ATP was reduced by 80%.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [45]
In the citing paper
“However, exocytosis is reduced by increasing concentrations of ADP with an IC50 of ~0.3 mM.”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [45]
In the citing paper
“ADP does not affect the release of RRP granules but interferes with granule mobilization/priming (45).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [45]
In the citing paper
“This is only 5-10% of that found in adrenal chromaffin cells, where the Ca2+ channel density is as high as 20 channels/μm2 (45).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [45]
Citations
Cites
Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 Å resolution
Sutton, R. B., Fasshauer, D., Jahn, R., & Brunger, A. T. (1998) · Nature · doi:10.1038/26412 · Cited by 2,417 · cited 1×
“What is the role of granular acidification in granule priming? Possibly, low granular pH promotes exocytosis by inducing conformational changes in SNARE proteins, rendering them more fusogenic (41).”
BackgroundDynamics of Insulin Secretion by the Perfused Rat Pancreas
CURRY, D. L., BENNETT, L. L., & GRODSKY, G. M. (1968) · Endocrinology · doi:10.1210/endo-83-3-572 · Cited by 601
Tight coupling between electrical activity and exocytosis in mouse glucagon-secreting alpha-cells.
Barg, S., Galvanovskis, J., Göpel, S. O., Rorsman, P., & Eliasson, L. (2000) · Diabetes · doi:10.2337/diabetes.49.9.1500 · Cited by 209
Self-citationPriming of insulin granules for exocytosis by granular Cl(-) uptake and acidification
Barg, S., Huang, P., Eliasson, L., Nelson, D. J., Obermüller, S., Rorsman, P., Thévenod, F., & Renström, E. (2001) · Journal of Cell Science · doi:10.1242/jcs.114.11.2145 · Cited by 194
Self-citation
Research works printed but not linked: 38
- Neher E, Zucker RS: Multiple calcium-dependent processes related to secretion in bovine chromaffin cells. Neuron 10: 21–30, 1993 · DOI
- Heinemann C, von Rüden L, Chow RH, Neher E: A two-step model of secretion control in neuroendocrine cells. Pflügers Arch 424:105–112, 1993 · DOI
- Parsons TD, Coorssen JR, Horstmann H, Almers W: Docked granules, the exocytic burst, and the need for ATP hydrolysis in endocrine cells. Neuron 15:1085–1096, 1995 · DOI
- Renström E, Eliasson L, Bokvist K, Rorsman P: Cooling inhibits exocytosis in single mouse pancreatic B-cells by suppression of granule mobilization. J Physiol 494:41–52, 1996 · DOI
- Eliasson L, Renström E, Ding WG, Proks P, Rorsman P: Rapid ATP-dependent priming of secretory granules precedes Ca2+-induced exocytosis in mouse pancreatic B-cells. J Physiol 503:399–412, 1997 · DOI · Paper page
- Gromada J, Høy M, Renström E, Bokvist K, Eliasson L, Göpel S, Rorsman P: CaM kinase II-dependent mobilization of secretory granules underlies acetylcholine-induced stimulation of exocytosis in mouse pancreatic B-cells. J Physiol 518:745–759, 1999 · DOI · Paper page
- Lang J: Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion. Eur J Biochem 259:3–17, 1999 · DOI · Paper page
- Efendic S, Wajngot A, Vranic M: Increased activity of the glucose cycle in the liver: early characteristic of type 2 diabetes. Proc Natl Acad Sci U S A 82:2965–2969, 1985 · DOI
- Wang H, Maechler P, Hagenfeldt KA, Wollheim CB: Dominant-negative suppression of HNF-1α function results in defective insulin gene transcription and impaired metabolism-secretion coupling in a pancreatic β-cell line. EMBO J 17:6701–6713, 1998 · DOI
- Gembal M, Gilon P, Henquin JC: Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells. J Clin Invest 89:1288–1295, 1992 · DOI · Paper page
- Rorsman P, Eliasson L, Renström E, Gromada J, Barg S, Göpel S: The cell physiology of biphasic insulin secretion. News Physiol Sci 15:72–77, 2000 · DOI
- Scepek S, Coorssen JR, Lindau M: Fusion pore expansion in horse eosinophils is modulated by Ca2+ and protein kinase C via distinct mechanisms. EMBO J 17:4340–4345, 1998 · DOI
- Barg S, Eliasson L, Galvanovskis J, Göpel SO, Obermüller S, Platzer J, Renström E, Trus M, Atlas D, Striessnig J, Rorsman P: Fast exocytosis with few Ca2+-channels in insulin-secreting mouse pancreatic B-cells. Biophys J In press
- Fenwick EM, Marty A, Neher E: Sodium and calcium channels in bovine chromaffin cells. J Physiol 331:599–635, 1982 · DOI · Paper page
- Klingauf J, Neher E: Modeling buffered Ca2+ diffusion near the membrane: implications for secretion in neuroendocrine cells. Biophys J 72:674–690, 1997 · DOI
- Voets T, Neher E, Moser T: Mechanisms underlying phasic and sustained secretion in chromaffin cells from mouse adrenal slices. Neuron 23:607–615, 1999 · DOI
- Bokvist K, Eliasson L, Ämmälä C, Renström E, Rorsman P: Co-localization of L-type Ca2+ channels and insulin-containing secretory granules and its significance for the initiation of exocytosis in mouse pancreatic B-cells. EMBO J 14:50–57, 1995 · DOI
- Wiser O, Bennett MK, Atlas D: Functional interaction of syntaxin and SNAP-25 with voltage-sensitive L- and N-type Ca2+ channels. EMBO J 15:4100–4110, 1996 · DOI
- Mochida S, Sheng ZH, Baker C, Kobayashi H, Catterall WA: Inhibition of neurotransmission by peptides containing the synaptic protein interaction site of N-type Ca2+ channels. Neuron 17:781–788, 1996 · DOI
- Ämmälä C, Eliasson L, Bokvist K, Larsson O, Ashcroft FM, Rorsman P: Exocytosis elicited by action potentials and voltage-clamp calcium currents in individual mouse pancreatic B-cells. J Physiol 472:665–688, 1993 · DOI · Paper page
- Gillis KD, Mossner R, Neher E: Protein kinase C enhances exocytosis from chromaffin cells by increasing the size of the readily releasable pool of secretory granules. Neuron 16:1209–1220, 1996 · DOI
- Neher E: Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release. Neuron 20:389–399, 1998 · DOI · Paper page
- Augustine GJ, Neher E: Calcium requirements for secretion in bovine chromaffin cells. J Physiol 450:247–271, 1992 · DOI
- Schneggenburger R, Neher E: Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406:889–893, 2000 · DOI
- Bollmann JH, Sakmann B, Borst JG: Calcium sensitivity of glutamate release in a calyx-type terminal. Science 289:953–957, 2000 · DOI
- Detimary P, Gilon P, Henquin JC: Interplay between cytoplasmic Ca2+ and the ATP/ADP ratio: a feedback control mechanism in mouse pancreatic islets. Biochem J 333:269–274, 1998 · DOI · Paper page
- von Gersdorff H, Vardi E, Matthews G, Sterling P: Evidence that vesicles on the synaptic ribbon of retinal bipolar neurons can be rapidly released. Neuron 16:1221–1227, 1996 · DOI
- Plattner H, Artalejo AR, Neher E: Ultrastructural organization of bovine chromaffin cell cortex-analysis by cryofixation and morphometry of aspects pertinent to exocytosis. J Cell Biol 139:1709–1717, 1997 · DOI
- Steyer JA, Horstmann H, Almers W: Transport, docking and exocytosis of single secretory granules in live chromaffin cells. Nature 388:474–478, 1997 · DOI
- Zimmerberg J, Whitaker M: Irreversible swelling of secretory granules during exocytosis caused by calcium. Nature 315:581–584, 1985 · DOI
- Day RN, Hinkle PM: Osmotic regulation of prolactin secretion: possible role of chloride. J Biol Chem 263:15915–15921, 1988 · DOI
- Woodbury DJ: Evaluation of the evidence for ion channels in synaptic vesicles. Mol Membr Biol 12:165–171, 1995 · DOI
- al Awqati Q, Barasch J, Landry D: Chloride channels of intracellular organelles and their potential role in cystic fibrosis. J Exp Biol 172:245–266, 1992 · DOI
- Maechler P, Wollheim CB: Mitochondrial glutamate acts as a messenger in glucose-induced insulin exocytosis. Nature 402:685–689, 1999 · DOI
- Fuller CM, Deetjen HH, Piiper A, Schulz I: Secretagogue and second messenger-activated Cl− permeabilities in isolated pancreatic zymogen granules. Pflügers Arch 415:29–36, 1989 · DOI
- Rupnik M, Zorec R: Cytosolic chloride ions stimulate Ca2+-induced exocytosis in melanotrophs. FEBS Lett 303:221–223, 1992 · DOI
- Stobrawa SM, Breiderhoff T, Takamori S, Engel D, Schweizer M, Zdebik AA, Bosl MR, Ruether K, Jahn H, Draguhn A, Jahn R, Jentsch TJ: Disruption of ClC-3, a chloride channel expressed on synaptic vesicles, leads to a loss of the hippocampus. Neuron 29:185–196, 2001 · DOI
- Daniel S, Noda M, Straub SG, Sharp GW: Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48:1686–1690, 1999 · DOI
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“24 REFERENCES [1] Barg S, Eliasson L, Renstrom E, Rorsman P: A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse betacells.”
BackgroundHyperinsulinism in Infancy: From Basic Science to Clinical Disease
Dunne, M. J., Cosgrove, K. E., Shepherd, R. M., Aynsley-Green, A., & Lindley, K. J. (2004) · Physiological Reviews · doi:10.1152/physrev.00022.2003 · Cited by 297
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“It has also been found that exocytosis is directly modulated by the ATP/ADP ratio [140], which could theoretically be detected by the granule SUR subunits.”
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Schulla, V., Renström, E., Feil, R., Feil, S., Franklin, I., Gjinovci, A., Jing, X., Laux, D., Lundquist, I., Magnuson, M. A., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg389 · Cited by 234
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Henquin, J. C., Ravier, M. A., Nenquin, M., Jonas, J., & Gilon, P. (2003) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.2003.01207.x · Cited by 180
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Jing, X., Li, D., Olofsson, C. S., Salehi, A. A., Surve, V. V., Caballero, J., Ivarsson, R., Lundquist, I., Pereverzev, A., Schneider, T., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522518 · Cited by 208
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Neurotransmitters and peptides: Whispered secrets and public announcements
Leng, G., & Ludwig, M. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.159103 · Cited by 168
“Depolarization can also produce large capacitance changes unrelated to exocytosis, reflecting gating charge movements associated with voltage-dependent conductances (Matthews, 1998; Barg et al. 2002).”
BackgroundInfluentialNevins, A. K., & Thurmond, D. (2003) · American Journal of Physiology - Cell Physiology · doi:10.1152/ajpcell.00093.2003 · Cited by 162
“The rate of replenishment of granule pools was recently demonstrated to be a critical factor in nutrientstimulated insulin secretion as opposed to the transient secretion elicited by KCl (3, 48).”
BackgroundTRPM4 controls insulin secretion in pancreatic β-cells
Cheng, H., Beck, A., Launay, P., Groß, S. A., Stokes, A. J., Kinet, J., Fleig, A., & Penner, R. (2006) · Cell Calcium · doi:10.1016/j.ceca.2006.04.032 · Cited by 181
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Henquin, J.-C., Nenquin, M., Stiernet, P., & Ahren, B. (2006) · Diabetes · doi:10.2337/diabetes.55.02.06.db05-1051 · Cited by 166
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“The Journal of biological chemistry 275: 39193-39199 [5] Barg S, Eliasson L, Renstrom E, Rorsman P (2002) A subset of 50 secretory granules in close contact with L-type Ca2+ channels accounts for first-phase insulin secretion in mouse beta-cells.”
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“In the B-cells, the ‘‘readily releasable pool’’ can be depleted in less than a second (Barg et al. 2001a & 2002a), whereas its refilling takes up to a minute (Gromada et al. 1999; Barg et al. 2002a).”
BackgroundSelf-citationHoboth, P., Müller, A., Ivanova, A., Mziaut, H., Dehghany, J., Sönmez, A., Lachnit, M., Meyer‐Hermann, M., Kalaidzidis, Y. L., & Solimena, M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1409542112 · Cited by 77
“The readily releasable pool consists of ∼50 SGs that are already docked at the plasma membrane (PM) before stimulation (11, 12).”
BackgroundOh, E., Kalwat, M. A., Kim, M.-J., Verhage, M., & Thurmond, D. C. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.361501 · Cited by 80
Ca2+ 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 94
Self-citationMouse models to study L-type calcium channel function
Moosmang, S., Lenhardt, P., Haider, N., Hofmann, F. B., & Wegener, J. W. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2004.12.003 · Cited by 80
Amplification of exocytosis by Ca2+‐induced Ca2+ release in INS‐1 pancreatic β cells
Kang, G., & Holz, G. G. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2002.029959 · Cited by 75
“These microdomains form at active zones where VDCCs are situated in close proximity to a small number of secretory granules constituting a docked, primed and readily releasable pool (Bokvist et al. 1995; Barg et al. 2001, 2002).”
BackgroundStraub, S. G., & Sharp, G. W. G. (2012) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00282.2011 · Cited by 78
Glucagon-Like Peptide 1 Regulates Sequential and Compound Exocytosis in Pancreatic Islet β-Cells
Kwan, E. P., & Gaisano, H. Y. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2734 · Cited by 76
MacDonald, P. E., Obermüller, S., Vikman, J., Galvanovskis, J., Rorsman, P., & Eliasson, L. (2005) · Diabetes · doi:10.2337/diabetes.54.3.736 · Cited by 70
“We also report that, like insulincontaining LDCVs (21), SLMV exocytosis is closely linked to Ca(2) entry through L-type channels, as indicated by the inhibitory action of isradipine.”
BackgroundSelf-citationHuman Insulin Vesicle Dynamics During Pulsatile Secretion
Michael, D. J., Xiong, W., Geng, X., Drain, P., & Chow, R. H. (2007) · Diabetes · doi:10.2337/db06-0367 · Cited by 69
“atic -cells, just 50 insulin vesicles are thought to be stored in the readily releasable pool (20,21), representing 1% of the 10,000 stored vesicles (22).”
BackgroundResultCollins, S. C., Hoppa, M. B., Walker, J. N., Amisten, S., Abdulkader, F., Bengtsson, M., Fearnside, J., Ramracheya, R., Toye, A. A., Zhang, Q., et al. (2010) · Diabetes · doi:10.2337/db09-0791 · Cited by 73
Self-citationChen, Y.-D., Wang, S., & Sherman, A. (2008) · Biophysical Journal · doi:10.1529/biophysj.107.124990 · Cited by 63
“This assumption is based on the finding that insulin-containing granules can form stable complexes with L-type channels (36,37) and on the realization that localized Ca(21)-influx plays an important role in insulin secretion (38).”
BackgroundReimann, F. M., Maziarz, M., Flock, G. B., Habib, A. M., Drucker, D. J., & Gribble, F. M. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.076414 · Cited by 71
“In pancreatic β-cells, a similar strong dependence of exocytosis on Ca2+ entry through L-type Ca2+ channels has been attributed to a physical interaction between the tail of the L-type Ca2+ channel and the exocytotic vesicles (Barg et al. 2002).”
BackgroundMacDonald, P. E., & Rorsman, P. (2007) · Physiology · doi:10.1152/physiol.00047.2006 · Cited by 61
Self-citationMartins, A., Jordan, V. C., Bochner, F., Chirayil, S., Paranawithana, N. N., Zhang, S.-R., Lo, S., Wen, X., Zhao, P.-Y., Neeman, M., et al. (2018) · Journal of the American Chemical Society · doi:10.1021/jacs.8b07607 · Cited by 65
Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta cells
Trexler, A., & Taraska, J. W. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.07.008 · Cited by 64
Suppressed Insulin Signaling and Increased Apoptosis inCd38-Null Islets
Johnson, J. D., Ford, E. L., Bernal‐Mizrachi, E., Kusser, K. L., Luciani, D. S., Han, Z., Tran, H. D., Randall, T. D., Lund, F. E., & Polonsky, K. S. (2006) · Diabetes · doi:10.2337/db05-1455 · Cited by 53
Structure and functional roles of Epac2 (Rapgef4)
Sugawara, K., Shibasaki, T., Takahashi, H., & Seino, S. (2016) · Gene · doi:10.1016/j.gene.2015.09.029 · Cited by 59
“The first and second phases are associated with exocytosis of insulin granules from the RRP and a reserve pool (RP), respectively (Henquin, 2000; Barg et al., 2002; Bratanova-Tochkova et al., 2002).”
BackgroundRegulation of two insulin granule populations within the reserve pool by distinct calcium sources
Hao, M., Li, X., Rizzo, M. A., Rocheleau, J. V., Dawant, B. M., & Piston, D. W. (2005) · Journal of Cell Science · doi:10.1242/jcs.02684 · Cited by 56
“%) exist in a functionally defined readily releasable pool (RRP) (Barg et al., 2002).”
BackgroundMunc18c Depletion Selectively Impairs the Sustained Phase of Insulin Release
Oh, E., & Thurmond, D. C. (2009) · Diabetes · doi:10.2337/db08-1059 · Cited by 64
“Granules located in the 50-nm group have been termed “morphologically docked” in the literature (18).”
BackgroundInfluentialExocytotic 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
Self-citationAction potentials and insulin secretion: new insights into the role of Kv channels
Jacobson, D. A., & Philipson, L. H. (2007) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2007.00784.x · Cited by 64
Uenishi, E., Shibasaki, T., Takahashi, H., Seki, C., Hamaguchi, H., Yasuda, T., Tatebe, M., Oiso, Y., Takenawa, T., & Seino, S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.464420 · Cited by 54
“It is generally thought that pancreatic -cells contain at least two pools of insulin secretory granules that differ in release competence as follows: a reserve pool (RP) that accounts for most of the granules, and a readily releasable pool (RRP) that accounts for the other 5% (9, 10).”
BackgroundKinetics of Rab27a‐dependent actions on vesicle docking and priming in pancreatic β‐cells
Merrins, M. J., & Stuenkel, E. L. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2008.158477 · Cited by 51
“…for first-phase insulin secretion (via KATP channel-dependent pathways), while the sustained second-phase release requires their refilling from a reserve pool (involving KATP channel-independent pathways) (Eliasson et al. 1996; Barg et al. 2001, 2002; Olofsson et al. 2002; Straub & Sharp, 2002).”
BackgroundThe Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis
Stephens, S. B., Edwards, R. J., Sadahiro, M., Lin, W., Jiang, C. S., Salton, S. R., & Newgard, C. B. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.050 · Cited by 66
Insulin granule trafficking in β-cells: mathematical model of glucose-induced insulin secretion
BERTUZZI, A., Salinari, S., & Mingrone, G. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00647.2006 · Cited by 50
“According to a well-established view (2, 48), within the pool of docked and primed granules here denoted by D, a pool of immediately releasable granules, DIR, must be distinguished.”
BackgroundInfluentialRecent Insights into Beta-cell Exocytosis in Type 2 Diabetes
Thurmond, D. C., & Gaisano, H. Y. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.12.012 · Cited by 53
Plasma membrane depolarization as a determinant of the first phase of insulin secretion
Hatlapatka, K., Willenborg, M., & Rustenbeck, I. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90981.2008 · Cited by 50
“This response is often regarded as being equivalent to the first phase of glucoseinduced insulin secretion (31), which conforms with the view that the first phase is due to a limited pool of secretion-ready granules requiring only one final signal that is provided by the [Ca(2) ]i elevation in the vicinity of voltage-…”
BackgroundRevisiting the role of SNAREs in exocytosis and membrane fusion
Szule, J. A., & Coorssen, J. R. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(03)00095-8 · Cited by 50
Goldspink, D. A., Lu, V. B., Billing, L., Larraufie, P., Tolhurst, G., Gribble, F. M., & Reimann, F. M. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.11.005 · Cited by 62
Insulin secretion and insulin-producing tumors
Guettier, J., & Görden, P. (2010) · Expert Review of Endocrinology & Metabolism · doi:10.1586/eem.09.83 · Cited by 49
The RalA GTPase Is a Central Regulator of Insulin Exocytosis from Pancreatic Islet Beta Cells
Lopez, J. A., Kwan, E. P., Xie, L., He, Y., James, D. E., & Gaisano, H. Y. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800321200 · Cited by 51
Komai, A. M., Brännmark, C., Musovic, S., & Olofsson, C. S. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.280388 · Cited by 49
“This rate is similar to what has been measured in pancreatic β-cells using the same intracellular solution (Proks et al. 1996; Barg et al. 2002; Olofsson et al. 2009).”
BackgroundResultEpidermal growth factor increases insulin secretion and lowers blood glucose in diabetic mice
Lee, H. Y., Yea, K., Kim, J., Lee, B. D., Chae, Y. C., Kim, H. S., Lee, D., Kim, S., Cho, J. ‐., Jin, C. J., et al. (2008) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2007.00169.x · Cited by 76
Vikman, J., Ma, X.-S., Hockerman, G., Rorsman, P., & Eliasson, L. (2006) · Journal of Molecular Endocrinology · doi:10.1677/jme.1.01978 · Cited by 46
“A subset of RRP vesicles appear tightly associated with the L-type voltagedependent Ca2+-channels and their fusion with the plasma membrane gives rise to a very fast component of exocytosis (immediately releasable pool, IRP; Barg et al. 2001, 2002).”
BackgroundSelf-citationMonitoring C-Peptide Storage and Secretion in Islet β-Cells In Vitro and In Vivo
Zhu, S., Larkin, D. D., Lu, S., Inouye, C. M., Haataja, L., Anjum, A., Kennedy, R., Castle, D. J., & Arvan, P. R. (2015) · Diabetes · doi:10.2337/db15-1264 · Cited by 43
Chen, X.-Y., Gu, X.-T., Saiyin, H., Wan, B., Zhang, Y.-J., Li, J., Wang, Y.-L., Gao, R., Wang, Y.-F., Dong, W.-P., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.375618 · Cited by 46
Ivarsson, R., Obermüller, S., Rutter, G. A., Galvanovskis, J., & Renström, E. (2004) · Traffic · doi:10.1111/j.1600-0854.2004.00216.x · Cited by 39
Glucose-dependent docking and SNARE protein-mediated exocytosis in mouse pancreatic alpha-cell
Andersson, S. A., Pedersen, M. G., Vikman, J., & Eliasson, L. (2011) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-011-0979-5 · Cited by 46
“A smaller fraction of the granules are suggested to be primed and belong to a readily releasable pool of granules (RRP) situated at the release site, in similarity to the situation in pancreatic beta-cells [1] and other neuroendocrine cells [23].”
Self-citationVikman, J., Svensson, H., Huang, Y., Kang, Y., Andersson, S. A., Gaisano, H. Y., & Eliasson, L. (2009) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.90585.2008 · Cited by 44
Self-citationDynamin Is Functionally Coupled to Insulin Granule Exocytosis
Min, L., Leung, Y., Tomás, A., Watson, R. T., Gaisano, H. Y., Halban, P. A., Pessin, J. E., & Hou, J. C. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703402200 · Cited by 40
The role of adherens junction proteins in the regulation of insulin secretion
Dissanayake, W. C., Sorrenson, B., & Shepherd, P. R. (2018) · Bioscience Reports · doi:10.1042/bsr20170989 · Cited by 42
Saito, T., Okada, S., Yamada, E., Ohshima, K., Shimizu, H., Shimomura, K., Sato, M., Pessin, J. E., & Mori, M. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305114200 · Cited by 37
Quesada, I., Chin, W., & Verdugo, P. (2003) · Biophysical Journal · doi:10.1016/s0006-3495(03)74535-4 · Cited by 39
“Al- though the mechanisms of acidification remain uncertain, the idea that pH changes may facilitate secretion by affecting exocytotic proteins, making them more fusogenic, has also been considered (Barg et al., 2001, 2002; Yang et al., 2002; Renstrom et al., 2002).”
BackgroundA fluorescent timer reporter enables sorting of insulin secretory granules by age
Yau, B., Hays, L. B., Liang, C., Laybutt, D. R., Thomas, H. E., Gunton, J. E., Williams, L. J., Hawthorne, W. J., Thorn, P., Rhodes, C. J., et al. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.012432 · Cited by 47
Modulation of Ionic Channels and Insulin Secretion by Drugs and Hormones in Pancreatic Beta Cells
Velasco, M., Díaz‐García, C. M., Larqué, C., & Hiriart, M. (2016) · Molecular Pharmacology · doi:10.1124/mol.116.103861 · Cited by 41
Signal integration at the level of ion channel and exocytotic function in pancreatic β-cells
MacDonald, P. E. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00426.2011 · Cited by 35
Pedersen, M. G., Tagliavini, A., & Henquin, J. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00380.2018 · Cited by 43
“117 118 Studies of exocytosis in single β-cells provided substantial support to the 119 pool model, with depletion of a readily releasable pool (RRP) yielding the first 120 phase, while refilling of the RRP creating the second phase (2, 10, 48, 58).”
BackgroundA Spatial Model of Insulin‐Granule Dynamics in Pancreatic β‐Cells
Dehghany, J., Hoboth, P., Ivanova, A., Mziaut, H., Müller, A., Kalaidzidis, Y. L., Solimena, M., & Meyer‐Hermann, M. (2015) · Traffic · doi:10.1111/tra.12286 · Cited by 21
Metadata
- Authors
- Barg, S., Eliasson, L., Renström, E., & Rorsman, P.
- Affiliations
- Lund University (SE)
- From the Department of Molecular and Cellular Physiology, Institute of Physiology, Lund University, Lund, Sweden
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2002-02-01
- Volume
- 51
- Issue
- suppl_1
- Pages
- S74-S82
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2050076638
- Cited by
- 227
- References
- 0
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 4 · 2019: 10 · 2018: 5 · 2017: 7 · 2016: 7 · 2015: 14 · 2014: 6 · 2013: 8 · 2012: 14
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- insulin secretion, secretory granules, L-type calcium channels, first-phase insulin secretion, second-phase insulin secretion, pancreatic beta cells, V-ATPase, ClC-3 chloride channel, ATP/ADP ratio
- MeSH terms
- Insulin Secretion, Animals, Insulin, Islets of Langerhans, Calcium Channels, L-Type, Secretory Vesicles, Mice
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