ArticleEMBO reports2014
BIG3 inhibits insulin granule biogenesis and insulin secretion.
Article in EMBO reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Genome-Wide Association Study Identifies Pharmacogenomic Variants Associated With Metformin Glycemic Response in African American Patients With Type 2 Diabetes.Diabetes care · 2024Pooled it
- Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.PLoS biology · 2023Article
- Condensation of the β-cell secretory granule luminal cargoes pro/insulin and ICA512 RESP18 homology domain.Protein science : a publication of the Protein Society · 2023Article
- Transcriptomic profiles of the ruminal wall in Italian Mediterranean dairy buffaloes fed green forage.BMC genomics · 2023Article
- Isolation and Proteomics of the Insulin Secretory Granule.Metabolites · 2021Review
- Normal and defective pathways in biogenesis and maintenance of the insulin storage pool.The Journal of clinical investigation · 2021Review
- Pathways of Glucagon Secretion and Trafficking in the Pancreatic Alpha Cell: Novel Pathways, Proteins, and Targets for Hyperglucagonemia.Frontiers in endocrinology · 2021Review
- GPCRs, G Proteins, and Their Impact on β-cell Function.Comprehensive Physiology · 2020Review
- In vivo identification of GTPase interactors by mitochondrial relocalization and proximity biotinylation.eLife · 2019Article
- Glucose-dependent phosphorylation signaling pathways and crosstalk to mitochondrial respiration in insulin secreting cells.Cell communication and signaling : CCS · 2019Article
- Hepatitis B X-interacting protein promotes the formation of the insulin gene-transcribing protein complex Pdx-1/Neurod1 in animal pancreatic β-cells.The Journal of biological chemistry · 2018Article
- Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics).Molecular & cellular proteomics : MCP · 2018Article
- Article
- miRNA-32 Drives Brown Fat Thermogenesis and Trans-activates Subcutaneous White Fat Browning in Mice.Cell reports · 2017Article
- Muscleblind-like 3 deficit results in a spectrum of age-associated pathologies observed in myotonic dystrophy.Scientific reports · 2016Article
- Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi.Cell reports · 2016Article
- Towards the construction of an interactome for Human WD40 protein family.Bioinformation · 2016Article
- Increased biogenesis of glucagon-containing secretory granules and glucagon secretion in BIG3-knockout mice.Molecular metabolism · 2015Article
- Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) is predicted to interact with its partner through an ARM-type α-helical structure.BMC research notes · 2014Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While molecular regulation of insulin granule exocytosis is relatively well understood, insulin granule biogenesis and maturation and its influence on glucose homeostasis are relatively unclear. Here, we identify a novel protein highly expressed in insulin-secreting cells and name it BIG3 due to its similarity to BIG/GBF of the Arf-GTP exchange factor (GEF) family. BIG3 is predominantly localized to insulin- and clathrin-positive trans-Golgi network (TGN) compartments. BIG3-deficient insulin-secreting cells display increased insulin content and granule number and elevated insulin secretion upon stimulation. Moreover, BIG3 deficiency results in faster processing of proinsulin to insulin and chromogranin A to β-granin in β-cells. BIG3-knockout mice exhibit postprandial hyperinsulinemia, hyperglycemia, impaired glucose tolerance, and insulin resistance. Collectively, these results demonstrate that BIG3 negatively modulates insulin granule biogenesis and insulin secretion and participates in the regulation of systemic glucose homeostasis.
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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 OpenQuestion graph.