Glucose Induces Opposite Intracellular Ca2+ Concentration Oscillatory Patterns in Identified α- and β-Cells Within Intact Human Islets of Langerhans
Open accessAbstract
Homeostasis of blood glucose is mainly regulated by the coordinated secretion of glucagon and insulin from α- and β-cells within the islets of Langerhans. The release of both hormones is Ca2+ dependent. In the current study, we used confocal microscopy and immunocytochemistry to unequivocally characterize the glucose-induced Ca2+ signals in α- and β-cells within intact human islets. Extracellular glucose stimulation induced an opposite response in these two cell types. Although the intracellular Ca2+ concentration ([Ca2+]i) in β-cells remained stable at low glucose concentrations, α-cells exhibited an oscillatory [Ca2+]i response. Conversely, the elevation of extracellular glucose elicited an oscillatory [Ca2+]i pattern in β-cells but inhibited low-glucose–induced [Ca2+]i signals in α-cells. These Ca2+ signals were synchronic among β-cells grouped in clusters within the islet, although they were not coordinated among the whole β-cell population. The response of α-cells was totally asynchronic. Therefore, both the α- and β-cell populations within human islets did not work as a syncitium in response to glucose. A deeper knowledge of α- and β-cell behavior within intact human islets is important to better understand the physiology of the human endocrine pancreas and may be useful to select high-quality islets for transplantation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Glucose-induced [Ca2+]i oscillations are observed in human β-cells and are less well synchronised across human islets than mouse islets.
“Although glucose-induced [Ca2+]i oscillations are observed in human β-cells, and are probably driven by oscillatory electrical activity (529) (Figure 6C), they are less well synchronised across human islets than mouse islets (102).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [529]
Synchronous [Ca2+]i oscillations across the whole islet are not usually observed in human islets, although they have been reported for small groups of β-cells.
“By contrast, synchronous [Ca2+]i oscillations across the whole islet are not usually observed in human islets (102), although they have been reported for small groups of β-cells (529).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [529]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Brissova, M., Fowler, M. J., Nicholson, W. E., Chu, A., Hirshberg, B., Harlan, D. M., & Powers, A. C. (2005) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.5c6684.2005 · Cited by 797 · see citing works
Santos, R. M., Rosario, L. M., Nadal, A., Garcia-Sancho, J., Soria, B., & Valdeolmillos, M. (1991) · Pfl�gers Archiv European Journal of Physiology · doi:10.1007/bf00550880 · Cited by 350 · cited 1× · see citing works
“The human islet contains a larger number of -cells than other species and a clustered distribution of the -cell population (4–6) instead of a continuous cell mass which, in the case of mice, leads to a functional syncitium (7,12,20).”
BackgroundSelf-citationTight 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 · see citing works
Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM
Dinneen, S., Alzaid, A., Turk, D., & Rizza, R. (1995) · Diabetologia · doi:10.1007/bf00400639 · Cited by 190 · see citing works
Gromada, J., Ma, X., Høy, M., Bokvist, K., Salehi, A., Berggren, P.-O., & Rorsman, P. (2004) · Diabetes · doi:10.2337/diabetes.53.suppl_3.s181 · Cited by 164 · see citing works
Liu, Y.-J., Vieira, E., & Gylfe, E. (2004) · Cell Calcium · doi:10.1016/j.ceca.2003.10.002 · Cited by 118 · see citing works
Quesada, I., Nadal, A., & Soria, B. (1999) · Diabetes · doi:10.2337/diabetes.48.12.2390 · Cited by 99 · see citing works
Self-citationOscillation of gap junction electrical coupling in the mouse pancreatic islets of Langerhans.
Andreu, E., Soria, B., & Sanchez-Andres, J. V. (1997) · The Journal of Physiology · doi:10.1113/jphysiol.1997.sp021899 · Cited by 58 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men
Rorsman, P., & Ashcroft, F. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00008.2017 · Cited by 793 · see citing works
Regulation of Insulin Secretion in Human Pancreatic Islets
Rorsman, P., & Braun, M. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183754 · Cited by 599 · see citing works
α-Cells of the Endocrine Pancreas: 35 Years of Research but the Enigma Remains
Gromada, J., Franklin, I., & Wollheim, C. B. (2007) · Endocrine Reviews · doi:10.1210/er.2006-0007 · Cited by 574 · see citing works
Structural similarities and differences between the human and the mouse pancreas
Dolenšek, J., Rupnik, M. S., & Stožer, A. (2015) · Islets · doi:10.1080/19382014.2015.1024405 · Cited by 342 · see citing works
Lipotoxicity disrupts incretin-regulated human β cell connectivity
Hodson, D. J., Mitchell, R. K., Bellomo, E. A., Sun, G., Vinet, L., Meda, P., Li, D., Li, W.-H., Bugliani, M., Marchetti, P., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci68459 · Cited by 210 · see citing works
Regulation of calcium in pancreatic α- and β-cells in health and disease
Rorsman, P., Braun, M., & Zhang, Q. (2012) · Cell Calcium · doi:10.1016/j.ceca.2011.11.006 · Cited by 220 · see citing works
Calcium signaling in pancreatic β-cells in health and in Type 2 diabetes.
Gilon, P., Chae, H., Rutter, G., & Ravier, M. (2014) · Cell Calcium · doi:10.1016/j.ceca.2014.09.001 · Cited by 212 · see citing works
The role of estrogen receptors in the control of energy and glucose homeostasis
Ropero, A. B., Alonso-Magdalena, P., Quesada, I., & Nadal, A. (2008) · Steroids · doi:10.1016/j.steroids.2007.12.018 · Cited by 170 · see citing works
Self-citationBenninger, R. K. P., Head, W. S., Zhang, M., Satin, L. S., & Piston, D. W. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.218909 · Cited by 165 · see citing works
“A small number of cells (5–10%) which were active at low glucose and were no longer active at elevated glucose are likely α-cells (Quesada et al. 2006), and were discounted from subsequent analysis (e.”
BackgroundFunctional Connectivity in Islets of Langerhans from Mouse Pancreas Tissue Slices
Stožer, A., Gosak, M., Dolenšek, J., Perc, M., Marhl, M., Rupnik, M. S., & Korošak, D. (2013) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002923 · Cited by 155 · see citing works
Physiology of the pancreatic α-cell and glucagon secretion: role in glucose homeostasis and diabetes
Quesada, I., Tudurí, E., Ripoll, C., & Nadal, Á. (2008) · Journal of Endocrinology · doi:10.1677/joe-08-0290 · Cited by 413 · see citing works
Self-citationHellman, B., Salehi, A. A., Gylfe, E., Dansk, H., & Grapengiesser, E. (2009) · Endocrinology · doi:10.1210/en.2009-0600 · Cited by 115 · see citing works
Glucose Suppression of Glucagon Secretion
Marchand, S. L., & Piston, D. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.069195 · Cited by 119 · see citing works
The physiological role of β-cell heterogeneity in pancreatic islet function
Benninger, R. K. P., & Kravets, V. V. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00568-0 · Cited by 136 · see citing works
Braun, M., Ramracheya, R., Amisten, S., Bengtsson, M., Moritoh, Y., Zhang, Q., Johnson, P. R. V., & Rorsman, P. (2009) · Diabetologia · doi:10.1007/s00125-009-1382-z · Cited by 104 · see citing works
Nanomaterial-mediated Biosensors for Monitoring Glucose
Taguchi, M., Ptitsyn, A. A., McLamore, E. S., & Claussen, J. C. (2014) · Journal of Diabetes Science and Technology · doi:10.1177/1932296814522799 · Cited by 139 · see citing works
Purinergic receptors in the endocrine and exocrine pancreas
Novak, I. (2008) · Purinergic Signalling Purinergic Signalling · doi:10.1007/s11302-007-9087-6 · Cited by 102 · see citing works
Glucose-Stimulated Calcium Dynamics in Islets of Langerhans in Acute Mouse Pancreas Tissue Slices
Stožer, A., Dolenšek, J., & Rupnik, M. S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054638 · Cited by 106 · see citing works
Autocrine regulation of insulin secretion
Braun, M., Ramracheya, R. D., & Rorsman, P. (2012) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2012.01642.x · Cited by 99 · see citing works
“However, the occurrence of [Ca2+]i oscillations in human islets is indicative of rhythmic action potential firing [95], and spontaneous and regular membrane potential oscillations are sometimes observed in isolated human β-cells (figure 4a).”
BackgroundKlemen, M. S., Dolenšek, J., Rupnik, M. S., & Stožer, A. (2017) · Islets · doi:10.1080/19382014.2017.1342022 · Cited by 95 · see citing works
González, A., Merino, B., Marroquí, L., Ñeco, P., Alonso-Magdalena, P., Caballero-Garrido, E., Vieira, E., Soriano, S., Gomis, R., Nadal, A., et al. (2013) · Endocrinology · doi:10.1210/en.2013-1424 · Cited by 92 · see citing works
Self-citationRorsman, 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
Vieira, E. C., Marroquí, L., Figueroa, A. L. C., Merino, B., Fernandez‐Ruiz, R., Nadal, Á., Burris, T. P., Gomis, R., & Quesada, I. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069939 · Cited by 78 · 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
Pulsatility of insulin release – a clinically important phenomenon
Hellman, B. (2009) · Upsala Journal of Medical Sciences · doi:10.3109/03009730903366075 · Cited by 77 · see citing works
Cohrs, C., Chen, C.-G., Jahn, S. R., Stertmann, J., Chmelova, H., Weitz, J., Bähr, A., Klymiuk, N., Steffen, A., Ludwig, B., et al. (2017) · Endocrinology · doi:10.1210/en.2016-1184 · Cited by 75 · see citing works
The Role of α-Cells in Islet Function and Glucose Homeostasis in Health and Type 2 Diabetes
Gilon, P. (2020) · Journal of Molecular Biology · doi:10.1016/j.jmb.2020.01.004 · Cited by 90 · see citing works
Mathematical 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
“6A) [4,25], which likely underlie slow oscillations in intracellular Ca [26,27] and pulsatile insulin release [28,29].”
BackgroundWestacott, M. J., Farnsworth, N. L., Clair, J. R. S., Poffenberger, G., Heintz, A., Ludin, N. W. F., Hart, N. J., Powers, A. C., & Benninger, R. K. P. (2017) · Diabetes · doi:10.2337/db17-0137 · Cited by 71 · see citing works
“Nevertheless, by studying islets from large numbers (32-76) of donors we Page 13 of 37 Diabetes”
BackgroundResultInhibitory Effects of Leptin on Pancreatic α-Cell Function
Tudurí, E., Marroquí, L., Soriano, S., Ropero, A. B., Batista, T. M., Piquer, S., López-Boado, M. Á., Carneiro, E. M., Gomis, R., Nadal, Á., et al. (2009) · Diabetes · doi:10.2337/db08-1787 · Cited by 78 · see citing works
Self-citationA Biophysical Model of Electrical Activity in Human β-Cells
Pedersen, M. G. (2010) · Biophysical Journal · doi:10.1016/j.bpj.2010.09.004 · Cited by 60 · see citing works
“This difference could be due to the involvement of different ion channels in human b-cells compared to rodents (1,3,14,15) or to differences in islet organization (16,17).”
BackgroundPancreatic β-cell heterogeneity in health and diabetes: classes, sources, and subtypes
Miranda, M. A., Macias-Velasco, J. F., & Lawson, H. A. (2021) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00649.2020 · Cited by 68 · see citing works
Tudurí, E., Filiputti, E., Carneiro, E. M., & Quesada, I. (2008) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00641.2007 · Cited by 47 · see citing works
Self-citationBeta-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
Irles, E., Ñeco, P., Lluesma, M., Villar-Pazos, S., Santos-Silva, J. C., Vettorazzi, J. F., Alonso‐Magdalena, P., Carneiro, E. M., Boschero, A. C., Nadal, Á., et al. (2015) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2015.01.033 · Cited by 53 · see citing works
“For the analysis of β-cell synchrony, whole islets were used to monitor changes in [Ca2+]i within individual cells using a confocal microscope (Zeiss LSM510 laser), as previously reported (Gonzalez et al., 2013; Quesada et al., 2006).”
InfluentialSelf-citationJahanshahi, P., Wu, R., Carter, J. D., & Nunemaker, C. S. (2008) · Endocrinology · doi:10.1210/en.2008-0773 · Cited by 53 · see citing works
Santos-Silva, J., Ribeiro, R. A., Vettorazzi, J., Irles, E., Rickli, S., Borck, P., Porciúncula, P. M., Quesada, I., Nadal, A., Boschero, A., et al. (2015) · Amino Acids · doi:10.1007/s00726-015-1988-z · Cited by 54 · see citing works
Self-citationParacrine regulation of glucagon secretion: the β/α/δ model
Watts, M., Ha, J., Kimchi, O., & Sherman, A. (2016) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00415.2015 · Cited by 53 · see citing works
Local and regional control of calcium dynamics in the pancreatic islet
Rutter, G., Hodson, D., Chabosseau, P., Haythorne, E., Pullen, T., & Leclerc, I. (2017) · Diabetes, obesity and metabolism · doi:10.1111/dom.12990 · Cited by 52 · see citing works
Heterogeneity of human pancreatic β-cells
Dominguez-Gutierrez, G., Xin, Y., & Gromada, J. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.015 · Cited by 49 · see citing works
Ojha, A., Ojha, U., Mohammed, R., Chandrashekar, A., & Ojha, H. (2019) · Clinical Pharmacology : Advances and Applications · doi:10.2147/cpaa.s202614 · Cited by 49 · see citing works
Fasting Hyperglycemia Impairs Glucose- But Not Insulin-Mediated Suppression of Glucagon Secretion
Abdul‐Ghani, M. A., & DeFronzo, R. A. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1515 · Cited by 46 · see citing works
Modeling the pancreatic α-cell: dual mechanisms of glucose suppression of glucagon secretion
Watts, M., & Sherman, A. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2013.11.4504 · Cited by 45 · see citing works
“Indeed, at least some a-cells must be active at high glucose to account for the antisynchronous pulses of insulin and glucagon observed in elevated glucose (43,59,60).”
BackgroundToward cell-based therapy of type I diabetes.
Kabelitz, D., Geissler, E., Soria, B., Schroeder, I., Fändrich, F., & Chatenoud, L. (2008) · Trends in immunology · doi:10.1016/j.it.2007.11.001 · Cited by 45 · see citing works
Self-citationInvestigating the Role of Islet Cytoarchitecture in Its Oscillation Using a New β-Cell Cluster Model
Nittala, A., Ghosh, S., & Wang, X. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000983 · Cited by 40 · see citing works
Kenty, J. H.-R., & Melton, D. A. (2015) · PLoS ONE · doi:10.1371/journal.pone.0122044 · Cited by 38 · see citing works
Mathematical modeling of gap junction coupling and electrical activity in human β -cells
Loppini, A., Braun, M., Filippi, S., & Pedersen, M. G. (2015) · Physical Biology · doi:10.1088/1478-3975/12/6/066002 · Cited by 39 · see citing works
Soriano, S., Gonzalez, A., Marroquí, L., Tudurí, E., Vieira, E., Amaral, A. G., Batista, T. M., Rafacho, A., Boschero, A. C., Nadal, A., et al. (2010) · Endocrinology · doi:10.1210/en.2010-0008 · Cited by 38 · see citing works
Self-citationCa2+ oscillations, waves, and networks in islets from human donors with and without type 2 diabetes
Gosak, M., Yan-Do, R., Lin, H.-P., Macdonald, P., & Stožer, A. (2021) · bioRxiv · doi:10.1101/2021.12.08.471749 · Cited by 33
“As recently reviewed elsewhere (12), previous studies involving [Ca]i imaging in human islets have reported globally (17, 18) or locally (19)”
MethodLeptin downregulates expression of the gene encoding glucagon in alphaTC1-9 cells and mouse islets
Marroquí, L., Vieira, E., González, A., Nadal, A., & Quesada, I. (2011) · Diabetologia · doi:10.1007/s00125-010-2024-1 · Cited by 30 · see citing works
Self-citationDolenšek, J., Spelic, D., Klemen, M. S., Žalik, B., Gosak, M., Rupnik, M. S., & Stožer, A. (2015) · Italian National Conference on Sensors · doi:10.3390/s151127393 · Cited by 27 · see citing works
Connexin-dependent signaling in neuro-hormonal systems
Potolicchio, I., Cigliola, V., Velázquez-García, S., Klee, P., Valjevac, A., Kapić, D., Ćosović, E., Lepara, O., Hadžović-Džuvo, A., Mornjacovic, Z., et al. (2011) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2011.09.022 · Cited by 25 · see citing works
Grubelnik, V., Zmazek, J., Markovič, R., Gosak, M., & Marhl, M. (2020) · Life · doi:10.3390/life10120348 · Cited by 28 · see citing works
Marinis, Y. Z. D., Zhang, E., Amisten, S., Taneera, J., Renström, E., Rorsman, P., & Eliasson, L. (2009) · Diabetologia · doi:10.1007/s00125-009-1635-x · Cited by 22 · see citing works
Ahangarpour, A., Heidari, H., Mard, S. A., Hashemitabar, M., & Khodadadi, A. (2014) · Iranian journal of pharmaceutical research · doi:10.22037/ijpr.2014.1546 · Cited by 23
Glucose induces synchronous mitochondrial calcium oscillations in intact pancreatic islets.
Quesada, I., Villalobos, C., Núñez, L., Chamero, P., Alonso, M., Nadal, A., & García-Sancho, J. (2008) · Cell Calcium · doi:10.1016/j.ceca.2007.03.001 · Cited by 23 · see citing works
Self-citationŠterk, M., Dolenšek, J., Bombek, L. K., Markovič, R., Zakelšek, D., Perc, M., Pohorec, V., Stožer, A., & Gosak, M. (2020) · Communications in Nonlinear Science and Numerical Simulation · doi:10.1016/j.cnsns.2020.105495 · Cited by 22 · see citing works
Stimulus-Secretion Coupling in Beta-Cells: From Basic to Bedside
Islam, M. S. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-12457-1_37 · Cited by 23 · see citing works
Model for Glucagon Secretion by Pancreatic α-Cells
González‐Vélez, V., Dupont, G., Gil, A., González, A., & Quesada, I. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032282 · Cited by 22 · see citing works
“This spontaneous behaviour has been widely observed in isolated a-cells [13,14], in clonal cell lines [16,18], and in intact islets [12].”
BackgroundSelf-citationAhangarpour, A., Alboghobeish, S., Oroojan, A. A., & Dehghani, M. (2018) · Human and Experimental Toxicology · doi:10.1177/0960327118769704 · Cited by 19
Confocal Laser Scanning Microscopy of Calcium Dynamics in Acute Mouse Pancreatic Tissue Slices.
Stožer, A., Dolenšek, J., Bombek, L. K., Pohorec, V., Rupnik, M. S., & Klemen, M. (2021) · Journal of Visualized Experiments · doi:10.3791/62293 · Cited by 18 · see citing works
Pancreatic islet cells: A model for calcium‐dependent peptide release
Soria, B., Tudurí, E., González, A., Hmadcha, A., Martín, F., Nadal, A., & Quesada, I. (2010) · HFSP Journal · doi:10.2976/1.3364560 · Cited by 16 · see citing works
“In addition, recent studies using redox confocal microscopy in intact islets have shown that glucose enhances the mitochondrial metabolism in -cells (Quesada et al., 2006b), further supporting the link between glucose metabolism and somatostatin release by means of KATP channels.”
BackgroundInfluentialSelf-citationStamper, I. J., & Wang, X. (2012) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2012.11.002 · Cited by 19 · see citing works
“For instance, some studies reported that rat islets (Manning Fox et al., 2006) and human islets (Cabrera et al., 2006; Quesada et al., 2006) exhibited less synchrony than mouse islets.”
BackgroundMarroquí, L., Batista, T. M., González, A., Vieira, E., Rafacho, A., Colleta, S., Taboga, S., Boschero, A., Nadal, A., Carneiro, E., et al. (2012) · Endocrinology · doi:10.1210/en.2011-1623 · Cited by 15 · see citing works
Self-citationHeterogeneous alpha-cell population modeling of glucose-induced inhibition of electrical activity
Montefusco, F., Cortese, G., & Pedersen, M. G. (2020) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2019.110036 · Cited by 13 · see citing works
“In alpha-cells in human islets glucose has been reported to lower Ca2+ levels (Quesada et al. (2006)).”
BackgroundHuman Beta Cell Functional Adaptation and Dysfunction in Insulin Resistance and Its Reversibility
Klemen, M. S., Kopecký, J., Dolenšek, J., & Stožer, A. (2023) · The Nephron journals/Nephron journals · doi:10.1159/000534667 · Cited by 11 · see citing works
“Some studies observed globally synchronized Ca 2+ oscillations similar to the ones in mouse islets [19], whereas others described only locally synchronized oscillations or did not quantify them in detail [2].”
BackgroundA computational systems analysis of factors regulating α cell glucagon secretion
Fridlyand, L. E., & Philipson, L. H. (2012) · Islets · doi:10.4161/isl.22193 · Cited by 12 · see citing works
Bru-Tari, E., Oropeza, D., & Herrera, P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.619150 · Cited by 11 · see citing works
Gil-Rivera, M., Medina-Gali, R., Martinez-Pinna, J., & Soriano, S. (2021) · International Review of Cell and Molecular Biology · doi:10.1016/bs.ircmb.2021.02.006 · Cited by 11 · see citing works
Singh, B., Khattab, F., & Gilon, P. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101495 · Cited by 10 · see citing works
Relation between diabetes mellitus, thyroid hormones and caffeine
da Silva, L. D., Wouk, J., Weber, V. M. R., Malfatti, C., & Osiecki, R. (2017) · Journal of Applied Pharmaceutical Science · doi:10.7324/japs.2017.70334 · Cited by 9 · see citing works
“The elevation of [Ca ++ ]i concentration stimulates the secretion of insulin, presumably by the liberation of the molecule storage in the β cells granules (Quesada et al., 2006).”
BackgroundGolfakhrabadi, F., Niknejad, M. R., Kalantari, H., Dehghani, M., Maram, N. S., & Ahangarpour, A. (2022) · Environmental science and pollution research international · doi:10.1007/s11356-022-23508-5 · Cited by 7
Sensing Intra‐ and Extra‐Cellular Ca2+ in the Islet of Langerhans
Huang, W.-K., Wu, T.-Z., Xie, C., Rayner, C., Priest, C., Ebendorff-Heidepriem, H., & Zhao, J. (2021) · Advanced Functional Materials · doi:10.1002/adfm.202106020 · Cited by 7 · see citing works
Pedersen, M. G., Salunkhe, V., Svedin, E., Edlund, A., & Eliasson, L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0103874 · Cited by 6 · see citing works
Physiological and Pathophysiological Control of Glucagon Secretion by Pancreatic α-Cells
Gilon, P., Cheng, R., Lai, B. K., Chae, H., & Gómez-Ruiz, A. (2014) · Springer eBooks · doi:10.1007/978-94-007-6884-0_37-2 · Cited by 8 · see citing works
The relationship between heart rate variability and glucose clearance in healthy men and women
Nickel, A., Buresh, R., McLester, C. N., Canino, A., Wilner, G., Vaughan, K., Chung, P., & Kliszczewicz, B. M. (2024) · PLoS ONE · doi:10.1371/journal.pone.0303346 · Cited by 5 · see citing works
Multilevel synchronization of human β-cells networks
Luchetti, N., Filippi, S., & Loppini, A. (2023) · Frontiers in Network Physiology · doi:10.3389/fnetp.2023.1264395 · Cited by 3 · see citing works
“Indeed, both electrical andmetabolic functional links were found within distances from a reference cell of about 20–50 μm, supporting the idea of significant coordination of cells activity in small groups (Quesada et al., 2006; Gosak et al., 2022).”
Saadati, M., & Jamali, Y. (2020) · Scientific Reports · doi:10.1038/s41598-021-89333-x · Cited by 5 · see citing works
Plasmonic imaging of living pancreatic beta-cell networks
Abayzeed, S., Galvis, D., Medel, K. R., Jones, C. F., González, O., Setchfield, K., Moreddu, R., Somekh, M. G., Wedgwood, K. C. A., & Smith, P. A. (2026) · Scientific Reports · doi:10.1038/s41598-025-34094-0 · Cited by 3 · see citing works
“Coordinated electrical oscillations in pancreatic cells are well known to underpin the secretion of insulin by pancreatic islets 44,48 .”
Pancreatic α-Cells and Insulin-Deficient Diabetes.
Quesada, I. (2016) · Endocrinology · doi:10.1210/en.2015-2088 · Cited by 4 · see citing works
Self-citationCell Networks in Endocrine/Neuroendocrine Gland Function
Guérineau, N. C., Campos, P., Tissier, P. L. L., Hodson, D., & Mollard, P. (2022) · Comprehensive Physiology · doi:10.1002/j.2040-4603.2022.tb00216.x · Cited by 3 · see citing works
Yuniwarti, E. Y. W., Saraswati, T. R., & Kusdiyantini, E. (2019) · Journal of Physics, Conference Series · doi:10.1088/1742-6596/1217/1/012162 · Cited by 3
Wagner, L. E., Melnyk, O., Muncy, A. N., Turner, A., Duffett, B. E., Muralidharan, C., Irizarry, M. M. M., Arvin, M. C., Orr, K. S., Wu, W., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.adx7770 · Cited by 7 · see citing works
Generation of pancreatic islets from stem cells
Soria, B., Pezzolla, D., López, J. E., Rojas, A., & Hmadcha, A. (2020) · Principles of Tissue Engineering · doi:10.1016/b978-0-12-398358-9.00041-0 · Cited by 2 · see citing works
Self-citationComputational methods to study Ca2+-triggered secretion at the cellular level
González-Vélez, V., Gil, A., & Dupont, G. (2012) · doi:10.6062/jcis.2012.03.01.0048 · Cited by 2
Glucose-driven intra- and inter-islet beta cell synchronization in pancreatic tissue slices
Bombek, L. K., Polšak, N., Dolenšek, J., Stožer, A., & Gosak, M. (2026) · Scientific Reports · doi:10.1038/s41598-026-46512-y · Cited by 1 · see citing works
Mathematical models and multiscale simulations of cellular secretion processes
González‐Vélez, V. (2011) · doi:10.5821/dissertation-2117-94768
“islets [83, 140], in isolated cells [143], or both [114, 142], or in cell lines [18].”
BackgroundMethodInfluentialVicente-Salar, N., Santana, A., Juan-Picó, P., Reig, J., & Roche, E. (2013) · Cytotherapy · doi:10.1016/j.jcyt.2012.08.002 · Cited by 1 · see citing works
DIABETES MELLITUS SECUNDÁRIA A PANCREATITE POR INTOXICAÇÃO ACIDENTAL POR CAFEÍNA EM CÃO
Tozato, M., Theodoro, S. D. S., dos Santos, M. V. P., Costa, P. D. C., Bento, I. T. C., Carciofí, A. C., & Camplesi, A. (2024) · Revista Foco · doi:10.54751/revistafoco.v17n5-092
Saadati, M., & Jamali, Y. (2020) · Research Square · doi:10.21203/rs.3.rs-132280/v1
Crosstalk Between Calcium and cAMP in Pancreatic Alpha Cells
Lorenzon, N., Imseis, J., Liang, L., Crane, C., Ikenouye, L., Pauckova, M., & Angleson, J. (2012) · doi:10.1016/j.bpj.2011.11.2799
“…in the form of glycogen and fat (Quesada et al, 2008; Quesada et al, 2006). α- 3 Cells release glucagon in response to a drop in blood glucose, which initiates glycogenolysis and gluconeogenesis leading to an increase in blood glucose (Quesada et al, 2008; Rorsman et al, 2008; Quesada et al, 2006).”
Background
- Authors
- Quesada, I., Todorova, M. G., Alonso-Magdalena, P., Beltrá, M., Carneiro, E. M., Martin, F., Nadal, A., & Soria, B.
- Affiliations
- Institute of Bioengineering, Miguel Hernandez University, Sant Joan d’Alacant, Spain
- Universitat de Miguel Hernández d'Elx (ES)
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Andalusian Center of Developmental Biology, University Pablo Olavide, Seville, Spain
- Centro Andaluz de Biología Molecular y Medicina Regenerativa (ES)
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-09-01
- Volume
- 55
- Issue
- 9
- Pages
- 2463-2469
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2159937109
- Cited by
- 104
- References
- 0
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 6 · 2014: 12 · 2013: 8 · 2012: 7
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion)
- Funders
- Instituto de Salud Carlos III (GO3/171, GO3/210, GO3/212)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Keywords
- calcium oscillations, alpha cells, pancreatic beta cells, glucose stimulation, insulin secretion, glucagon secretion, calcium signaling, islet transplantation, pancreatic endocrine cells
- MeSH terms
- Adolescent, Adult, Calcium, Glucose, Humans, Immunohistochemistry, Microscopy, Confocal, Calcium Signaling, Glucagon-Secreting Cells, Insulin-Secreting Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
