ArticleDiabetes2012
Doc2b is a key effector of insulin secretion and skeletal muscle insulin sensitivity.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
40 citing papers in PubMed, 48 citations in OpenAlex.
- Increased CA3 burst activity inbioRxiv : the preprint server for biology · 2026Article
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- GLUT4 Trafficking and Storage Vesicles: Molecular Architecture, Regulatory Networks, and Their Disruption in Insulin Resistance.International journal of molecular sciences · 2025Review
- doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish.BMC biology · 2025Article
- DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets.Metabolism: clinical and experimental · 2025Article
- Pancreatic β-cells package double C2-like domain beta protein into extracellular vesicles via tandem C2 domains.Frontiers in endocrinology · 2024Article
- A Novel Role for DOC2B in Ameliorating Palmitate-Induced Glucose Uptake Dysfunction in Skeletal Muscle Cells via a Mechanism Involving β-AR Agonism and Cofilin.International journal of molecular sciences · 2023Article
- Role of the voltage-gated proton channel Hv1 in insulin secretion, glucose homeostasis, and obesity.Journal of physiology and biochemistry · 2022Review
- Convergent copy number increase of genes associated with freshwater colonization in fishes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2022Article
- DOC2b Enhances β-Cell Function via a Novel Tyrosine Phosphorylation-Dependent Mechanism.Diabetes · 2022Article
- Exocytosis Proteins: Typical and Atypical Mechanisms of Action in Skeletal Muscle.Frontiers in endocrinology · 2022Review
- Conventional and Unconventional Mechanisms by which Exocytosis Proteins Oversee β-cell Function and Protection.International journal of molecular sciences · 2021Review
- Gut microbiome mediates host genomic effects on phenotypes: a case study with fat deposition in pigs.Computational and structural biotechnology journal · 2021Article
- Article
- Distinct insulin granule subpopulations implicated in the secretory pathology of diabetes types 1 and 2.eLife · 2020Article
- Structure, function and regulation of mammalian glucose transporters of the SLC2 family.Pflugers Archiv : European journal of physiology · 2020Review
- Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake.Comprehensive Physiology · 2020Review
- Doc2 Proteins Are Not Required for the Increased Spontaneous Release Rate in Synaptotagmin-1-Deficient Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Recent Insights into Beta-cell Exocytosis in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Synaptotagmin-1 and Doc2b Exhibit Distinct Membrane-Remodeling Mechanisms.Biophysical journal · 2020Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Exocytosis of intracellular vesicles, such as insulin granules, is carried out by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) and Sec1/Munc18 (SM) proteins. An additional regulatory protein, Doc2b (double C2 domain), has recently been implicated in exocytosis from clonal β-cells and 3T3-L1 adipocytes. Here, we investigated the role of Doc2b in insulin secretion, insulin sensitivity, and the maintenance of whole-body glucose homeostasis. Doc2b heterozygous (Doc2b(+/-)) and homozygous (Doc2b(-/-)) knockout mice exhibited significant whole-body glucose intolerance and peripheral insulin resistance, compared with wild-type littermates. Correspondingly, Doc2b(+/-) and Doc2b(-/-) mice exhibited decreased responsiveness of pancreatic islets to glucose in vivo, with significant attenuation of both phases of insulin secretion ex vivo. Peripheral insulin resistance correlated with ablated insulin-stimulated glucose uptake and GLUT4 vesicle translocation in skeletal muscle from Doc2b-deficient mice, which was coupled to impairments in Munc18c-syntaxin 4 dissociation and in SNARE complex assembly. Hence, Doc2b is a key positive regulator of Munc18c-syntaxin 4-mediated insulin secretion as well as of insulin responsiveness in skeletal muscle, and thus a key effector for glucose homeostasis in vivo. Doc2b's actions in glucose homeostasis may be related to its ability to bind Munc18c and/or directly promote fusion of insulin granules and GLUT4 vesicles in a stimulus-dependent manner.
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What Socratic holds
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.