ArticleThe Journal of biological chemistry2012
Munc18-1 regulates first-phase insulin release by promoting granule docking to multiple syntaxin isoforms.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Functional differences of Munc18 isoforms reflect their affinities for the exocytosis site.Cellular and molecular life sciences : CMLS · 2026Article
- Biphasic glucose-stimulated insulin secretion over decades: a journey from measurements and modeling to mechanistic insights.Life metabolism · 2025Review
- A hydrophobic groove in secretagogin allows for alternate interactions with SNAP-25 and syntaxin-4 in endocrine tissues.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- KCNH6 channel promotes insulin exocytosis via interaction with Munc18-1 independent of electrophysiological processes.Cellular and molecular life sciences : CMLS · 2024Article
- Modulation of insulin secretion by RBFOX2-mediated alternative splicing.Nature communications · 2023Article
- STXBP6 Gene Mutation: A New Form of SNAREopathy Leads to Developmental Epileptic Encephalopathy.International journal of molecular sciences · 2023Article
- Hypoxia causes pancreatic β-cell dysfunction and impairs insulin secretion by activating the transcriptional repressor BHLHE40.EMBO reports · 2023Article
- Rapid Quantification of First and Second Phase Insulin Secretion Dynamics using an In vitro Platform for Improving Insulin Therapy.Cell calcium · 2023Article
- Epigallocatechin gallate inhibits SNARE-dependent membrane fusion by blocking trans-SNARE assembly.FEBS open bio · 2022Article
- Enrichment of the exocytosis protein STX4 in skeletal muscle remediates peripheral insulin resistance and alters mitochondrial dynamics via Drp1.Nature communications · 2022Article
- Collagen IV-β1-Integrin Influences INS-1 Cell Insulin SecretionFrontiers in cell and developmental biology · 2022Article
- Exocytosis in Astrocytes.Biomolecules · 2021Review
- Article
- Role of Munc18-1 in the biological functions and pathogenesis of neurological disorders (Review).Molecular medicine reports · 2021Review
- Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection.International journal of molecular sciences · 2021Review
- A requirement for PAK1 to support mitochondrial function and maintain cellular redox balance via electron transport chain proteins to prevent β-cell apoptosis.Metabolism: clinical and experimental · 2021Article
- CASK modulates the assembly and function of the Mint1/Munc18-1 complex to regulate insulin secretion.Cell discovery · 2020Article
- Distinct insulin granule subpopulations implicated in the secretory pathology of diabetes types 1 and 2.eLife · 2020Article
- Essential Role of Syntaxin-Binding Protein-1 in the Regulation of Glucagon-Like Peptide-1 Secretion.Endocrinology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Attenuated levels of the Sec1/Munc18 (SM) protein Munc18-1 in human islet β-cells is coincident with type 2 diabetes, although how Munc18-1 facilitates insulin secretion remains enigmatic. Herein, using conventional Munc18-1(+/-) and β-cell specific Munc18-1(-/-) knock-out mice, we establish that Munc18-1 is required for the first phase of insulin secretion. Conversely, human islets expressing elevated levels of Munc18-1 elicited significant potentiation of only first-phase insulin release. Insulin secretory changes positively correlated with insulin granule number at the plasma membrane: Munc18-1-deficient cells lacked 35% of the normal component of pre-docked insulin secretory granules, whereas cells with elevated levels of Munc18-1 exhibited a ∼20% increase in pre-docked granule number. Pre-docked syntaxin 1-based SNARE complexes bound by Munc18-1 were detected in β-cell lysates but, surprisingly, were reduced by elevation of Munc18-1 levels. Paradoxically, elevated Munc18-1 levels coincided with increased binding of syntaxin 4 to VAMP2 at the plasma membrane. Accordingly, syntaxin 4 was a requisite for Munc18-1 potentiation of insulin release. Munc18c, the cognate SM isoform for syntaxin 4, failed to bind SNARE complexes. Given that Munc18-1 does not pair with syntaxin 4, these data suggest a novel indirect role for Munc18-1 in facilitating syntaxin 4-mediated granule pre-docking to support first-phase insulin exocytosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.