CoChat
Sign Up
Cited by 43Pancreatic function and diabetesCellular transport and secretionDiabetes and associated disorders

Glucose principally regulates insulin secretion in mouse islets by controlling the numbers of granule fusion events per cell

Open access
Low, Jiun T., Mitchell, Justin M., Do, Oanh H., Bax, Jacinda, Rawlings, Alicia, Zavortink, Michael, Morgan, Garry, Parton, Robert G. +2 more·2013·Diabetologia
DOI 10.1007/s00125-013-3019-5PMC PMC3825531
Open this paper in CoChat — free accountOpen PDF

Abstract

AIMS/HYPOTHESIS: In dispersed single beta cells the response of each cell to glucose is heterogeneous. In contrast, within an islet, cell-to-cell communication leads to glucose inducing a more homogeneous response. For example, increases in NAD(P)H and calcium are relatively uniform across the cells of the islet. These data suggest that secretion of insulin from single beta cells within an islet should also be relatively homogeneous. The aim of this study was to test this hypothesis by determining the glucose dependence of single-cell insulin responses within an islet. METHODS: Two-photon microscopy was used to detect the glucose-induced fusion of single insulin granules within beta cells in intact mouse islets. RESULTS: First, we validated our assay and showed that the measures of insulin secretion from whole islets could be explained by the time course and numbers of granule fusion events observed. Subsequent analysis of the patterns of granule fusion showed that cell recruitment is a significant factor, accounting for a fourfold increase from 3 to 20 mmol/l glucose. However, the major factor is the regulation of the numbers of granule fusion events within each cell, which increase ninefold over the range of 3 to 20 mmol/l glucose. Further analysis showed that two types of granule fusion event occur: 'full fusion' and 'kiss and run'. We show that the relative frequency of each type of fusion is independent of glucose concentration and is therefore not a factor in the control of insulin secretion. CONCLUSIONS/INTERPRETATION: Within an islet, glucose exerts its main effect through increasing the numbers of insulin granule fusion events within a cell.

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.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1007/s00125-013-3019-5

Cites

8 of 8 references verified0 citation errors · 0 not checkable

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.

A few free checks a day · papers already verified open instantly · results are public

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?

  • In intact mouse islets, secretory capacity varies considerably between β-cells.

    “Imaging of exocytosis in intact mouse islets indicates that in fact the secretory capacity varies considerably between β-cells (402).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [402]

    The Results (section ‘Increasing glucose concentration drives increases in the number of responding cells and granule fusion events within a cell’; page unavailable) report that more cells show fusion events as glucose rises, supporting some heterogeneity in observed responses. But the authors caution that apparently non-responding cells may have fused granules outside the imaged area, and the Discussion emphasizes coordinated responses across cells. The imaging therefore does not establish that intrinsic secretory capacity varies considerably between β-cells. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The islet's response to glucose is also due to recruitment of an increasing number of β-cells.

    “Thus, although every β-cell has the capacity to respond to glucose in a graded fashion, the islet’s response to glucose is also due to recruitment of an increasing number of β-cells (283, 402).”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [402]

  • Increasing glucose recruits quiescent β-cells and causes a concentration-dependent increase in electrical activity of individual β-cells.

    “Although increasing glucose ‘recruits’ quiescent β-cells (402, 761), there is also a concentration-dependent increase in the electrical activity of individual β-cells.”

    From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [402]

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

Flagged first, then by citations

Research works printed but not linked: 34

  1. [1]Schuit FC Tveld PAI Pipeleers DG Glucose stimulates proinsulin biosynthesis by a dose-dependent recruitment of pancreatic beta-cells Proc Natl Acad Sci U S A 1988 85 3865 3869 10.1073/pnas.85.11.3865 3287379 PMC280320 · DOI · Paper page
  2. [2]Schuit FC Kiekens R Pipeleers DG Measuring the balance between insulin synthesis and insulin release Biochem Biophys Res Comm 1991 178 1182 1187 10.1016/0006-291X(91)91017-7 1872837 · DOI
  3. [3]Heimberg H Devos A Vandercammen A Vanschaftingen E Pipeleers D Schuit F Heterogeneity in glucose sensitivity among pancreatic beta-cells is correlated to differences in glucose phosphorylation rather than glucose-transport EMBO J 1993 12 2873 2879 8335003 PMC413540
  4. [4]Jonkers FC Henquin JC Measurements of cytoplasmic Ca2+ in islet cell clusters show that glucose rapidly recruits beta-cells and gradually increases the individual cell response Diabetes 2001 50 540 550 10.2337/diabetes.50.3.540 11246873 · DOI
  5. [5]Salomon D Meda P Heterogeneity and contact-dependent regulation of hormone-secretion by individual b-cells Exp Cell Res 1986 162 507 520 10.1016/0014-4827(86)90354-X 3510882 · DOI
  6. [6]Gembal M Gilon P Henquin JC Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse β-cells J Clin Invest 1992 89 1288 1295 10.1172/JCI115714 1556189 PMC442990 · DOI · Paper page
  7. [7]Pipeleers D Kiekens R Ling Z Wilikens A Schuit F Physiological relevance of heterogeneity in the pancreatic beta cell population Diabetologia 1994 37 Suppl S57 S64 10.1007/BF00400827 7821741 · DOI
  8. [8]deVargas LM Sobolewski J Siegel R Moss LG Individual beta cells within the intact islet differentially respond to glucose J Biol Chem 1997 272 26573 26577 10.1074/jbc.272.42.26573 9334237 · DOI
  9. [10]Halban PA Wollheim CB Blondel B Meda P Niesor EN Mintz DH The possible importance of contact between pancreatic-islet cells for the control of insulin release Endocrinology 1982 111 86 94 10.1210/endo-111-1-86 6123433 · DOI
  10. [13]Bennett BD Jetton TL Ying GT Magnuson MA Piston DW Quantitative subcellular imaging of glucose metabolism within intact pancreatic islets J Biol Chem 1996 271 3647 3651 10.1074/jbc.271.7.3647 8631975 · DOI
  11. [14]Benninger RKP Zhang M Head WS Satin LS Piston DW Gap junction coupling and calcium waves in the pancreatic islet Biophys J 2008 95 5048 5061 10.1529/biophysj.108.140863 18805925 PMC2586567 · DOI
  12. [16]Ashcroft FM Rorsman P Diabetes mellitus and the beta cell: the last ten years Cell 2012 148 1160 1171 10.1016/j.cell.2012.02.010 22424227 PMC5890906 · DOI · Paper page
  13. [17]Henquin JC Nenquin M Stiernet P Ahren B In vivo and in vitro glucose-induced biphasic insulin secretion in the mouse—pattern and role of cytoplasmic Ca2+ and amplification signals in beta-cells Diabetes 2006 55 441 451 10.2337/diabetes.55.02.06.db05-1051 16443779 · DOI · Paper page
  14. [18]MacDonald PE Braun M Galvanovskis J Rorsman P Release of small transmitters through kiss-and-run fusion pores in rat pancreatic beta cells Cell Metab 2006 4 283 290 10.1016/j.cmet.2006.08.011 17011501 · DOI
  15. [19]Tsuboi T McMahon HT Rutter GA Mechanisms of dense core vesicle recapture following ‘kiss and run’ (‘cavicapture’) exocytosis in insulin-secreting cells J Biol Chem 2004 279 47115 47124 10.1074/jbc.M408179200 15331588 · DOI
  16. [20]Doreian BW Fulop TG Meklemburg RL Smith CB Cortical f-actin, the exocytic mode, and neuropeptide release in mouse chromaffin cells is regulated by myristoylated alanine-rich c-kinase substrate and myosin II Mol Biol Cell 2009 20 3142 3154 10.1091/mbc.E09-03-0197 19420137 PMC2704164 · DOI
  17. [21]Ma L Bindokas VP Kuznetsov A Direct imaging shows that insulin granule exocytosis occurs by complete vesicle fusion Proc Natl Acad Sci U S A 2004 101 9266 9271 10.1073/pnas.0403201101 15197259 PMC438965 · DOI
  18. [22]Takahashi N Kishimoto T Nemoto T Kadowaki T Kasai H Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet Science 2002 297 1349 1352 10.1126/science.1073806 12193788 · DOI
  19. [23]Thorn P Fogarty KE Parker I Zymogen granule exocytosis is characterized by long fusion pore openings and preservation of vesicle lipid identity Proc Natl Acad Sci U S A 2004 101 6774 6779 10.1073/pnas.0400336101 15090649 PMC404121 · DOI
  20. [24]Kim A Miller K Jo J Kilimnik G Wojcik P Hara M Islet architecture a comparative study Islets 2009 1 129 136 10.4161/isl.1.2.9480 20606719 PMC2894473 · DOI
  21. [25]Kwan EP Gaisano HY Glucagon-like peptide 1 regulates sequential and compound exocytosis in pancreatic islet beta-cells Diabetes 2005 54 2734 2743 10.2337/diabetes.54.9.2734 16123364 · DOI
  22. [26]Hoppa MB Jones E Karanauskaite J Multivesicular exocytosis in rat pancreatic beta cells Diabetologia 2012 55 1001 1012 10.1007/s00125-011-2400-5 22189485 PMC3296018 · DOI
  23. [27]Bock T Svenstrup K Pakkenberg B Buschard K Unbiased estimation of total beta-cell number and mean beta-cell volume in rodent pancreas APMIS 1999 107 791 799 10.1111/j.1699-0463.1999.tb01474.x 10515130 · DOI
  24. [28]Huang L Shen H Atkinson MA Kennedy RT Detection of exocytosis at individual pancreatic beta-cells by amperometry at a chemically-modified microelectrode Proc Natl Acad Sci U S A 1995 92 9608 9612 10.1073/pnas.92.21.9608 7568182 PMC40851 · DOI · Paper page
  25. [29]Ohara-Imaizumi M Nakamichi Y Tanaka T Katsuta H Ishida H Nagamatsu S Monitoring of exocytosis and endocytosis of insulin secretory granules in the pancreatic beta-cell line MIN6 using pH-sensitive green fluorescent protein (pHluorin) and confocal laser microscopy Biochem J 2002 363 73 80 10.1042/0264-6021:3630073 11903049 PMC1222453 · DOI
  26. [30]Behrendorff N Floetenmeyer M Schwiening C Thorn P Protons released during pancreatic acinar cell secretion acidify the lumen and contribute to pancreatitis in mice Gastroenterology 2010 139 1711 1719 10.1053/j.gastro.2010.07.051 20691184 · DOI
  27. [31]Reetz A Solimena M Matteoli M Folli F Takei K Decamilli P GABA and pancreatic beta-cells: colocalization of glutamic-acid decarboxylase (GAD) and GABA with synaptic-like microvesicles suggests their role in GABA storage and secretion EMBO J 1991 10 1275 1284 2022191 PMC452782
  28. [32]Gopel SO Kanno T Barg S Rorsman P Patch-clamp characterisation of somatostatin secreting delta-cells in intact mouse pancreatic islets J Physiol 2000 528 497 507 10.1111/j.1469-7793.2000.00497.x 11060127 PMC2270149 · DOI
  29. [33]Rutter GA Tsuboi T Kiss and run exocytosis of dense core secretory vesicles Neuroreport 2004 15 79 81 10.1097/00001756-200401190-00016 15106835 · DOI
  30. [35]Braun M Wendt A Karanauskaite J Corelease and differential exit via the fusion pore of GABA, serotonin, and ATP from LDCV in rat pancreatic beta cells J Gen Physiol 2007 129 221 231 10.1085/jgp.200609658 17296927 PMC2151613 · DOI · Paper page
  31. [36]Olofsson CS Collins S Bengtsson M Long-term exposure to glucose and lipids inhibits glucose-induced insulin secretion downstream of granule fusion with plasma membrane Diabetes 2007 56 1888 1897 10.2337/db06-1150 17456851 · DOI · Paper page
  32. [37]Klueh U Liu ZH Cho B Continuous glucose monitoring in normal mice and mice with prediabetes and diabetes Diabetes Techn Therap 2006 8 402 412 10.1089/dia.2006.8.402 16800762 · DOI
  33. [38]Juntunen KS Niskanen LK Liukkonen KH Poittanen KS Holst JJ Mykkanen HM Postprandial glucose, insulin, and incretin responses to grain products in healthy subjects Am J Clin Nutr 2002 75 254 262 11815315
  34. [41]Jacques-Silva MC Correa-Medina M Cabrera O ATP-gated P2X(3) receptors constitute a positive autocrine signal for insulin release in the human pancreatic beta cell Proc Natl Acad Sci U S A 2010 107 6465 6470 10.1073/pnas.0908935107 20308565 PMC2851966 · DOI · Paper page

Cited by

Sorted by citations

Authors
Low, J. T., Mitchell, J. M., Do, O. H., Bax, J., Rawlings, A., Zavortink, M., Morgan, G., Parton, R. G., Gaisano, H. Y., & Thorn, P.
Affiliations
  • The University of Queensland (AU)
  • University of Toronto (CA)
Corresponding author
Thorn, Peter
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2013-09-01
Volume
56
Issue
12
Pages
2629-2637
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-013-3019-5
PMC
PMC3825531
OpenAlex
W1980744914
Cited by
43
References
8
Citations by year
2024: 4 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 1 · 2018: 7 · 2017: 2 · 2016: 5 · 2015: 8 · 2014: 3 · 2013: 2
FWCI
5.92
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Medical Research Council
  • Australian Research Council (DP110100642)
  • National Health and Medical Research Council (1002520)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
insulin secretion, glucose regulation, pancreatic beta cells, kiss-and-run, cell recruitment, islet heterogeneity, cell-to-cell communication, two-photon microscopy, mouse islets
MeSH terms
Insulin Secretion, Animals, Blood Glucose, Cell Membrane, Exocytosis, Glucose, Insulin, Islets of Langerhans, Membrane Fusion, Mice, Inbred Strains, Microscopy, Fluorescence, Models, Biological, Mice

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