Cited by 211Pancreatic function and diabetesCellular transport and secretionCalcium signaling and nucleotide metabolism

The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.

Imaging analysis reveals mechanistic differences between first- and second-phase insulin exocytosis

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Abstract

The mechanism of glucose-induced biphasic insulin release is unknown. We used total internal reflection fluorescence (TIRF) imaging analysis to reveal the process of first- and second-phase insulin exocytosis in pancreatic β cells. This analysis showed that previously docked insulin granules fused at the site of syntaxin (Synt)1A clusters during the first phase; however, the newcomers fused during the second phase external to the Synt1A clusters. To reveal the function of Synt1A in phasic insulin exocytosis, we generated Synt1A-knockout (Synt1A−/−) mice. Synt1A−/− β cells showed fewer previously docked granules with no fusion during the first phase; second-phase fusion from newcomers was preserved. Rescue experiments restoring Synt1A expression demonstrated restoration of granule docking status and fusion events. Inhibition of other syntaxins, Synt3 and Synt4, did not affect second-phase insulin exocytosis. We conclude that the first phase is Synt1A dependent but the second phase is not. This indicates that the two phases of insulin exocytosis differ spatially and mechanistically.

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  1. 2004, Am. J. Med. Genet. A., 131, 255
  2. 1986, Lancet., 2, 360
  3. 1997, Am. J. Hum. Genet., 61, 449
  4. 2000, News Physiol. Sci., 15, 72

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Metadata

Authors
Ohara-Imaizumi, M., Fujiwara, T., Nakamichi, Y., Okamura, T., Akimoto, Y., Kawai, J., Matsushima, S., Kawakami, H., Watanabe, T., Akagawa, K., & Nagamatsu, S.
Affiliations
  • 1Department of Biochemistry
  • 2Department of Cell Physiology
  • 5Division of Animal Models, Department of Infectious Diseases, Research Institute, International Medical Center of Japan, Tokyo 162-8655, Japan
  • 3Department of Anatomy,
  • Juntendo University (JP)
  • Kyorin University (JP)
Corresponding author
Nagamatsu, Shinya
Venue
The Journal of Cell Biology
Published
2007-05-14
Volume
177
Issue
4
Pages
695-705
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
OpenAlex
W2124167615
Cited by
211
References
46
Citations by year
2026: 2 · 2025: 6 · 2024: 4 · 2023: 9 · 2022: 7 · 2021: 10 · 2020: 6 · 2019: 7 · 2018: 6 · 2017: 13 · 2016: 5 · 2015: 11 · 2014: 16 · 2013: 10 · 2012: 23
FWCI
18.64
Type
journal article
Language
en
Open access
Licence
cc-by-nc-sa
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
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 exocytosis, first-phase insulin secretion, second-phase insulin secretion, syntaxin 1A, syntaxin 3, syntaxin 4, granule fusion, pancreatic beta cells, glucose-induced insulin release
MeSH terms
Insulin Secretion, Animals, Cells, Cultured, Exocytosis, Insulin, Islets of Langerhans, Male, Microscopy, Fluorescence, Mice, Knockout, Mice

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