Munc13-1 is required for the sustained release of insulin from pancreatic β cells
Open accessAbstract
Munc13-1 is a presynaptic protein that is essential for synaptic vesicle priming. Deletion of Munc13-1/unc13 causes total arrest of synaptic transmission due to a complete loss of fusion-competent synaptic vesicles. The requirement of Munc13-1 for large dense-core vesicles (LDCVs), however, has not been established. In the present study, we use Munc13-1 knockout (KO) and diacylglycerol (DAG) binding-deficient Munc13-1(H567K) mutant knockin (KI) mice to determine the role of Munc13-1 in the secretion of insulin-containing LDCVs from primary cultured pancreatic beta cells. We show that Munc13-1 is required for the sustained insulin release upon prolonged stimulation. The sustained release involves signaling of DAG second messenger, since it is also reduced in KI mice. Insulin secretion in response to glucose stimulation is characterized by a biphasic time course. Our data show that Munc13-1 plays an essential role in the development of the second phase of insulin secretion by priming insulin-containing LDCVs.
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Ablation of munc13-1 selectively suppresses 2nd phase insulin secretion.
“The role of munc13-2 in the β-cell has not been studied, but ablation of munc13-1 selectively suppresses 2nd phase insulin secretion (333).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [333]
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Dynamics of Insulin Secretion by the Perfused Rat Pancreas
CURRY, D. L., BENNETT, L. L., & GRODSKY, G. M. (1968) · Endocrinology · doi:10.1210/endo-83-3-572 · Cited by 601 · see citing works
Fast insulin secretion reflects exocytosis of docked granules in mouse pancreatic B-cells
Olofsson, C. S., Göpel, S. O., Barg, S., Galvanovskis, J., Ma, X., Salehi, A., Rorsman, P., & Eliasson, L. (2002) · Pflügers Archiv · doi:10.1007/s00424-002-0781-5 · Cited by 290 · see citing works
Regulated Exocytosis of GABA-containing Synaptic-like Microvesicles in Pancreatic β-cells
Braun, M., Wendt, A., Birnir, B., Broman, J., Eliasson, L., Galvanovskis, J., Gromada, J., Mulder, H., & Rorsman, P. (2004) · The Journal of General Physiology · doi:10.1085/jgp.200308966 · Cited by 130 · see citing works
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- [1]1. Arkhammar, P. ∙ Juntti-Berggren, L. ∙ Larsson, O. ... Protein kinase C modulates the insulin secretory process by maintaining a proper function of the beta-cell voltage-activated Ca2+ channels J. Biol. Chem. 1994; 269:2743-2749
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Pancreatic regulation of glucose homeostasis.
Röder, P. V., Wu, B., Liu, Y., & Han, W. (2016) · Experimental & Molecular Medicine · doi:10.1038/emm.2016.6 · Cited by 985 · see citing works
The role of incretins in glucose homeostasis and diabetes treatment
Kim, W., & Egan, J. M. (2008) · Pharmacological Reviews · doi:10.1124/pr.108.000604 · Cited by 824 · see citing works
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
Wang, Z., & Thurmond, D. C. (2009) · Journal of Cell Science · doi:10.1242/jcs.034355 · Cited by 386 · see citing works
Speese, S., Petrie, M., Schuske, K., Ailion, M., Ann, K., Iwasaki, K., Jorgensen, E. M., & Martin, T. F. J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1466-07.2007 · Cited by 333 · see citing works
Glucose-Dependent Granule Docking Limits Insulin Secretion and Is Decreased in Human Type 2 Diabetes
Gandasi, N. R., Yin, P., Omar-Hmeadi, M., Ottosson Laakso, E., Vikman, P., & Barg, S. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.12.017 · Cited by 115 · see citing works
Leung, Y. M., Kwan, E. P., Ng, B., Kang, Y., & Gaisano, H. Y. (2007) · Endocrine Reviews · doi:10.1210/er.2007-0010 · Cited by 106 · see citing works
- Authors
- Kang, L., He, Z., Xu, P., Fan, J., Betz, A., Brose, N., & Xu, T.
- Affiliations
- Huazhong University of Science and Technology (CN)
- Chinese Academy of Sciences (CN)
- Max Planck Institute of Experimental Medicine (DE)
- Corresponding author
- Xu, Tao
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2006-06
- Volume
- 3
- Issue
- 6
- Pages
- 463-468
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2113055773
- Cited by
- 96
- References
- 3
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2022: 7 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 2 · 2017: 8 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- 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 › Physiology › Calcium signaling and nucleotide metabolism
- Keywords
- Munc13-1, insulin secretion, pancreatic beta cells, sustained insulin release, large dense core vesicles, synaptic vesicle priming, diacylglycerol signaling, second-phase insulin secretion, glucose-stimulated insulin secretion, vesicle fusion, knockout mice
- MeSH terms
- Insulin Secretion, Animals, Animals, Newborn, Calcium, Cells, Cultured, Diglycerides, Exocytosis, Glucose, Insulin, Nerve Tissue Proteins, Time Factors, Signal Transduction, Mice, Knockout, Secretory Vesicles, Insulin-Secreting Cells, Mice
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