ArticleProceedings of the National Academy of Sciences of the United States of America2015
Synaptotagmin-7 phosphorylation mediates GLP-1-dependent potentiation of insulin secretion from β-cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Gene expression regulation by CaCellular & molecular biology letters · 2026Pooled it
- Article
- GLP-1 receptor and Mitochondria-ER Contact Sites: an emerging mechanism of metabolic regulation.Frontiers in physiology · 2026Review
- A pancreas-hippocampus feedback mechanism regulates circadian changes in depression-related behaviors.Nature neuroscience · 2025Article
- The complex web of membrane contact sites in brain aging and neurodegeneration.Cellular and molecular life sciences : CMLS · 2025Review
- Synaptotagmin-7 deficit causes insulin hypoactivity and contributes to behavioral alterations in mice.iScience · 2025Article
- The lysosomal trafficking regulator "LYST": an 80-year traffic jam.Frontiers in immunology · 2024Review
- Direct Differentiation of Bone Marrow Mononucleated Cells Into Insulin-Producing Cells Using 4 Specific Soluble Factors.Stem cells translational medicine · 2023Article
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.PLoS biology · 2023Article
- Excessive iron inhibits insulin secretion via perturbing transcriptional regulation of SYT7 by OGG1.Cellular and molecular life sciences : CMLS · 2023Article
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- Epigallocatechin gallate inhibits SNARE-dependent membrane fusion by blocking trans-SNARE assembly.FEBS open bio · 2022Article
- Multiplexed microfluidic platform for stem-cell derived pancreatic islet β cells.Lab on a chip · 2022Article
- Reduced calcium levels and accumulation of abnormal insulin granules in stem cell models of HNF1A deficiency.Communications biology · 2022Article
- 14-3-3-zeta mediates GLP-1 receptor agonist action to alter α cell proglucagon processing.Science advances · 2022Article
- Development of Type 1 Diabetes may occur through a Type 2 Diabetes mechanism.Frontiers in endocrinology · 2022Article
- β-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High-Fat Diet-Fed Mice.Diabetes · 2021Article
- Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection.International journal of molecular sciences · 2021Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Glucose stimulates insulin secretion from β-cells by increasing intracellular Ca(2+). Ca(2+) then binds to synaptotagmin-7 as a major Ca(2+) sensor for exocytosis, triggering secretory granule fusion and insulin secretion. In type-2 diabetes, insulin secretion is impaired; this impairment is ameliorated by glucagon-like peptide-1 (GLP-1) or by GLP-1 receptor agonists, which improve glucose homeostasis. However, the mechanism by which GLP-1 receptor agonists boost insulin secretion remains unclear. Here, we report that GLP-1 stimulates protein kinase A (PKA)-dependent phosphorylation of synaptotagmin-7 at serine-103, which enhances glucose- and Ca(2+)-stimulated insulin secretion and accounts for the improvement of glucose homeostasis by GLP-1. A phospho-mimetic synaptotagmin-7 mutant enhances Ca(2+)-triggered exocytosis, whereas a phospho-inactive synaptotagmin-7 mutant disrupts GLP-1 potentiation of insulin secretion. Our findings thus suggest that synaptotagmin-7 is directly activated by GLP-1 signaling and may serve as a drug target for boosting insulin secretion. Moreover, our data reveal, to our knowledge, the first physiological modulation of Ca(2+)-triggered exocytosis by direct phosphorylation of a synaptotagmin.
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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.