Cited by 89Pancreatic function and diabetesCellular transport and secretionDiabetes and associated disorders

Insulin secretion from beta cells in intact mouse islets is targeted towards the vasculature

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Low, Jiun T., Zavortink, Michael, Mitchell, Justin M., Gan, Wan J., Do, Oanh Hoang, Schwiening, Christof J., Gaisano, Herbert Y., Thorn, Peter·2014·Diabetologia

Abstract

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).”
  • 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).”

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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
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
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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