Insulin secretion from beta cells in intact mouse islets is targeted towards the vasculature
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AIMS/HYPOTHESIS: We set out to test the hypothesis that insulin secretion from beta cells is targeted towards the vasculature. METHODS: The spatial location of granule fusion was identified by live-cell two-photon imaging of mouse pancreatic beta cells within intact islets, using sulforhodamine B labelling. Three-dimensional (3D) immunofluorescence of pancreatic slices was used to identify the location of proteins associated with neuronal synapses. RESULTS: We demonstrated an asymmetric, non-random, distribution of sites of insulin granule fusion in response to glucose and focal targeting of insulin granule secretion to the beta cell membrane facing the vasculature. 3D immunofluorescence of islets showed that structural proteins, such as liprin, piccolo and Rab2-interacting molecule, normally associated with neuronal presynaptic targeting, were present in beta cells and enriched at the vascular face. In contrast, we found that syntaxin 1A and synaptosomal-associated protein 25 kDa (SNAP25) were relatively evenly distributed across the beta cells. CONCLUSIONS/INTERPRETATION: Our results show that beta cells in situ, within intact islets, are polarised and target insulin secretion. This evidence for an 'endocrine synapse' has wide implications for our understanding of stimulus-secretion coupling in healthy islets and in disease.
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The scaffolding proteins RIM2 and piccolo, but not the SNARE proteins, localise to the capillary regions.
“There is evidence that insulin granule exocytosis is targeted towards the capillaries and that the ‘scaffolding’ proteins RIM2 and piccolo (but not the SNARE proteins) localise to these regions (403).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [403]
Insulin granule exocytosis is targeted towards the capillaries.
“There is evidence that insulin granule exocytosis is targeted towards the capillaries and that the ‘scaffolding’ proteins RIM2 and piccolo (but not the SNARE proteins) localise to these regions (403).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [403]
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Fu, J., Githaka, J. M., Dai, X.-Q., Plummer, G., Suzuki, K., Spigelman, A. F., Bautista, A., Kim, R., Greitzer-Antes, D., Fox, J. E. M., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.127896 · Cited by 24 · see citing works
Self-citationAdhesion G-protein coupled receptors: Implications for metabolic function
Olaniru, O. E., & Persaud, S. J. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.012 · Cited by 23 · see citing works
Glucose but not KCl diminishes submembrane granule turnover in mouse beta-cells
Brüning, D., Reckers, K., Drain, P. F., & Rustenbeck, I. (2017) · Journal of Molecular Endocrinology · doi:10.1530/jme-17-0063 · Cited by 20 · see citing works
Improved Multiprotein Microcontact Printing on Plasma Immersion Ion Implanted Polystyrene
Kosobrodova, E., Gan, W. J., Kondyurin, A. V., Thorn, P., & Bilek, M. (2017) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.7b15545 · Cited by 20 · see citing works
Self-citationRole of the active zone protein, ELKS, in insulin secretion from pancreatic β-cells
Ohara-Imaizumi, M., Aoyagi, K., & Ohtsuka, T. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.017 · Cited by 21 · see citing works
Rediscovering Primary Cilia in Pancreatic Islets
Lee, E. Y., & Hughes, J. W. (2023) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2022.0442 · Cited by 17 · see citing works
Cortical mitochondria regulate insulin secretion by local Ca2+ buffering in rodent beta cells
Griesche, N., Sanchez, G., Hermans, C., & Idevall‐Hagren, O. (2019) · Journal of Cell Science · doi:10.1242/jcs.228544 · Cited by 16 · see citing works
Functional analysis of islet cells in vitro, in situ, and in vivo
Li, W.-H. (2020) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2020.02.002 · Cited by 15 · see citing works
Makhmutova, M., Liang, T., Gaisano, H. Y., Caicedo, A., & Almaça, J. (2017) · Journal of Visualized Experiments · doi:10.3791/56089 · Cited by 14 · see citing works
Self-citationBarillaro, M., Schuurman, M., & Wang, R. (2022) · Endocrinology · doi:10.1210/endocr/bqac179 · Cited by 13 · see citing works
Presynaptic-like mechanisms and the control of insulin secretion in pancreatic β-cells.
Deng, K., & Thorn, P. (2022) · Cell Calcium · doi:10.1016/j.ceca.2022.102585 · Cited by 13 · see citing works
Self-citationCohrs, C. M., Chen, C., Atkinson, M. A., Drotar, D. M., & Speier, S. (2023) · Diabetes · doi:10.2337/dbi20-0018 · Cited by 13 · see citing works
The importance of being edgy: cell geometric edges as an emerging polar domain in plant cells
Elliott, L., & Kirchhelle, C. (2019) · Journal of Microscopy · doi:10.1111/jmi.12847 · Cited by 12 · see citing works
Release of insulin granules by simultaneous, high‐speed correlative SICM‐FCM
Bednarska, J., Novák, P., Korchev, Y. E., Rorsman, P., Tarasov, A. I., & Shevchuk, A. (2020) · Journal of Microscopy · doi:10.1111/jmi.12972 · Cited by 11 · see citing works
Imaging Analysis of Insulin Secretion with Two-Photon Microscopy
Takahashi, N. K. (2015) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b14-00880 · Cited by 11 · see citing works
Probes for monitoring regulated exocytosis
Li, W.-H. (2017) · Cell Calcium · doi:10.1016/j.ceca.2017.01.002 · Cited by 10 · see citing works
The changing view of insulin granule mobility: From conveyor belt to signaling hub
Gaus, B., Brüning, D., Groß, S., Müller, M., & Rustenbeck, I. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.983152 · Cited by 10 · see citing works
Do, O. H., Low, J. T., & Thorn, P. (2015) · Journal of Visualized Experiments · doi:10.3791/52632 · Cited by 10 · see citing works
Self-citationInforming β-cell regeneration strategies using studies of heterogeneity
Nasteska, D., Viloria, K., Everett, L., & Hodson, D. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.06.004 · Cited by 9 · see citing works
Jevon, D., Cottle, L., Hallahan, N., Harwood, R., Samra, J. S., Gill, A. J., Loudovaris, T., Thomas, H. E., & Thorn, P. (2024) · Diabetologia · doi:10.1007/s00125-024-06180-x · Cited by 9 · see citing works
Self-citationpeng, X., Wang, K., & Chen, L. (2024) · Life Metabolism · doi:10.1093/lifemeta/loae038 · Cited by 9 · see citing works
Kinetics of functional beta cell mass decay in a diphtheria toxin receptor mouse model of diabetes
van Krieken, P. P., Dicker, A., Eriksson, M., Herrera, P. L., Ahlgren, U., Berggren, P., & Ilegems, E. (2017) · Scientific Reports · doi:10.1038/s41598-017-12124-w · Cited by 9 · see citing works
The Role of Alpha Cells in the Self-Assembly of Bioengineered Islets
Wieland, F. C., Sthijns, M. M. J. P. E., Geuens, T., van Blitterswijk, C., & LaPointe, V. L. S. (2020) · Tissue Engineering Part A · doi:10.1089/ten.tea.2020.0080 · Cited by 8 · see citing works
Cell Networks in Endocrine/Neuroendocrine Gland Function
Guérineau, N. C., Campos, P., Tissier, P. L., Hodson, D. J., & Mollard, P. (2022) · Comprehensive physiology · doi:10.1002/cphy.c210031 · Cited by 8 · see citing works
Cilia Action in Islets: Lessons From Mouse Models
Jung, H.-C., & Hughes, J. W. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.922983 · Cited by 6 · see citing works
Fye, M. A., Sangowdar, P., Jayathilake, A., Regan, P. H., Gu, G., & Kaverina, I. (2025) · Molecular Biology of the Cell · doi:10.1091/mbc.e24-10-0487 · Cited by 6 · see citing works
Insulin secretion hot spots in pancreatic β cells as secreting adhesions
Fye, M. A., & Kaverina, I. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1211482 · Cited by 6 · see citing works
Microfluidic vascular formation model for assessing angiogenic capacities of single islets
Nashimoto, Y., Konno, A., Imaizumi, T., Nishikawa, K., Ino, K., Hori, T., Kaji, H., Shintaku, H., Goto, M., & Shiku, H. (2023) · Biotechnology and Bioengineering · doi:10.1002/bit.28631 · Cited by 6 · see citing works
Biomimetic Surfaces Supporting Dissociated Pancreatic Islet Cultures
Andersen, P. L., & Vermette, P. (2017) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2017.07.060 · Cited by 6 · see citing works
Islet cilia and glucose homeostasis
Melena, I., & Hughes, J. W. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.1082193 · Cited by 6 · see citing works
Novel aspects of intra-islet communication: Primary cilia and filopodia.
Moruzzi, N., Leibiger, B., Barker, C. J., Leibiger, I., & Berggren, P. (2022) · Advances in Biological Regulation · doi:10.1016/j.jbior.2022.100919 · Cited by 5 · see citing works
Amin, M. L., Deng, K., Tran, H. A., Singh, R., Rnjak‐Kovacina, J., & Thorn, P. (2022) · Bioengineering · doi:10.3390/bioengineering9120722 · Cited by 3 · see citing works
Self-citationHeterogeneity and altered β-cell identity in the TallyHo model of early-onset type 2 diabetes
McDonald, S. D., Ray, P., Bunn, R. C., Fowlkes, J. L., Thrailkill, K. M., & Popescu, I. R. (2022) · Acta Histochemica · doi:10.1016/j.acthis.2022.151940 · Cited by 2 · see citing works
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Odongo, K., Ishinaka, M., Abe, A., Harada, N., Yamaji, R., Yamashita, Y., & Ashida, H. (2025) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.202400690 · Cited by 2 · see citing works
Imaging endocrinology in animal models of endocrine disease
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Cottle, L., Gilroy, I., Deng, K., Loudovaris, T., Thomas, H. E., Gill, A. J., Samra, J. S., Kebede, M. A., Kim, J., & Thorn, P. (2021) · Metabolites · doi:10.3390/metabo11060363 · Cited by 2 · see citing works
Self-citationLocal Integrin Activation in Pancreatic ß Cells Targets Insulin Secretion to the VasculaturePreprint
Gan, W. J., Do, O. H., Cottle, L., Kosobrodova, E., Cooper-White, J. J., Bilek, M., & Thorn, P. (2018) · SSRN Electronic Journal · doi:10.2139/ssrn.3155818 · Cited by 2 · see citing works
Self-citationSubmembrane liprin-α1 clusters spatially localize insulin granule fusion
Deng, K., Sun, K., Hallahan, N., Gan, W. J., Cielesh, M., Mahyad, B., Kebede, M. A., Larance, M., & Thorn, P. (2025) · The Journal of Cell Biology · doi:10.1083/jcb.202410210 · Cited by 1 · see citing works
Self-citationMuhammed, Y., Ramirez, A. B., & Lazenby, R. A. (2026) · ACS Measurement Science Au · doi:10.1021/acsmeasuresciau.5c00192 · Cited by 1 · see citing works
Primary cilia sensitize insulin receptor-mediated negative feedback in pancreatic β cellsPreprint
Li, Y., Shrestha, P. K., & Wu, Y. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.12.02.408914 · Cited by 1 · see citing works
McLaughlin, M. R., Weaver, S. A., Syed, F., & Evans‐Molina, C. (2023) · Comprehensive physiology · doi:10.1002/cphy.c230002 · Cited by 1 · see citing works
Do, O. H., & Thorn, P. (2016)
Self-citationБактериялық коллагеназалар - шолу мақаласы
Kostanova, A., & Baltin, K. (2024) · Journal of biological research. · doi:10.70264/jbr.v1.4.2024.5
A Comprehensive Workflow for Imaging Live Insulin Secretion Events and Granules in Intact IsletsPreprint
Fye, M. A., Sharma, R., Myat, P. S. M., Regan, P. H., McKinney, H., Gu, G., & Kaverina, I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.22.650066
Deng, K., Sun, K., Webster, H., Yau, B., Loudovaris, T., Thomas, H. E., Kebede, M. A., & Thorn, P. (2025) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2025.111036
Self-citationBarmaver, S. N., Hamilton, N., Gu, G., & Kaverina, I. (2026) · Molecular Metabolism · doi:10.1016/j.molmet.2026.102408
Amira, I., & Hasib, A. (2026) · Exploration of Endocrine and Metabolic Diseases · doi:10.37349/eemd.2026.101484
- Authors
- Low, J. T., Zavortink, M., Mitchell, J. M., Gan, W. J., Do, O. H., Schwiening, C. J., Gaisano, H. Y., & Thorn, P.
- Affiliations
- The University of Queensland (AU)
- University of Cambridge (GB)
- University of Toronto (CA)
- Corresponding author
- Thorn, Peter
- Venue
- Diabetologia
- Published
- 2014-05-05
- Volume
- 57
- Issue
- 8
- Pages
- 1655-1663
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC4079948
- OpenAlex
- W1980283412
- Cited by
- 89
- References
- 49
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 7 · 2022: 14 · 2021: 7 · 2020: 8 · 2019: 9 · 2018: 7 · 2017: 11 · 2016: 4 · 2015: 7
- FWCI
- 7.28
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Diabetologia (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Directorate for Biological Sciences
- Medical Research Council
- Australian Research Council (DP110100642)
- National Health and Medical Research Council (1002520, 1059426)
- National Medical Research Council
- 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, pancreatic beta cells, pancreatic islets, vascular targeting, presynaptic proteins, piccolo, syntaxin 1A, SNAP-25, glucose stimulation, stimulus-secretion coupling
- MeSH terms
- Insulin Secretion, Animals, Exocytosis, Glucose, Insulin, Synapses, Insulin-Secreting Cells, Synaptosomal-Associated Protein 25, Mice
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