ArticleDiabetologia2014
DOC2 isoforms play dual roles in insulin secretion and insulin-stimulated glucose uptake.
Article in Diabetologia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Investigating the shared genetic architecture between schizophrenia and body mass index.Molecular psychiatry · 2023Pooled it
- DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets.Metabolism: clinical and experimental · 2025Article
- 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
- Article
- 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
- Phosphatidylinositol 4,5-bisphosphate drives CaThe Journal of biological chemistry · 2019Article
- Protein kinase C iota facilitates insulin-induced glucose transport by phosphorylation of soluble nSF attachment protein receptor regulator (SNARE) double C2 domain protein b.Journal of diabetes investigation · 2019Article
- DOC2B promotes insulin sensitivity in mice via a novel KLC1-dependent mechanism in skeletal muscle.Diabetologia · 2019Article
- Article
- Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation.The Journal of biological chemistry · 2018Article
- Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2018Article
- High dietary fat and sucrose results in an extensive and time-dependent deterioration in health of multiple physiological systems in mice.The Journal of biological chemistry · 2018Article
- Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men.Physiological reviews · 2018Review
- BAIAP3, a C2 domain-containing Munc13 protein, controls the fate of dense-core vesicles in neuroendocrine cells.The Journal of cell biology · 2017Article
- Key proteins involved in insulin vesicle exocytosis and secretion.Biomedical reports · 2017Article
- Increased Expression of the Diabetes Gene SOX4 Reduces Insulin Secretion by Impaired Fusion Pore Expansion.Diabetes · 2016Article
- Doc2b serves as a scaffolding platform for concurrent binding of multiple Munc18 isoforms in pancreatic islet β-cells.The Biochemical journal · 2014Article
- Re-sequencing data for refining candidate genes and polymorphisms in QTL regions affecting adiposity in chicken.PloS one · 2014Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisGlucose-stimulated insulin secretion (GSIS) and insulin-stimulated glucose uptake are processes that rely on regulated intracellular vesicle transport and vesicle fusion with the plasma membrane. DOC2A and DOC2B are calcium-sensitive proteins that were identified as key components of vesicle exocytosis in neurons. Our aim was to investigate the role of DOC2 isoforms in glucose homeostasis, insulin secretion and insulin action.
methodsDOC2 expression was measured by RT-PCR and western blotting. Body weight, glucose tolerance, insulin action and GSIS were assessed in wild-type (WT), Doc2a (-/-) (Doc2aKO), Doc2b (-/-) (Doc2bKO) and Doc2a (-/-)/Doc2b (-/-) (Doc2a/Doc2bKO) mice in vivo. In vitro GSIS and glucose uptake were assessed in isolated tissues, and exocytotic proteins measured by western blotting. GLUT4 translocation was assessed by epifluorescence microscopy.
resultsDoc2b mRNA was detected in all tissues tested, whereas Doc2a was only detected in islets and the brain. Doc2aKO and Doc2bKO mice had minor glucose intolerance, while Doc2a/Doc2bKO mice showed pronounced glucose intolerance. GSIS was markedly impaired in Doc2a/Doc2bKO mice in vivo, and in isolated Doc2a/Doc2bKO islets in vitro. In contrast, Doc2bKO mice had only subtle defects in insulin secretion in vivo. Insulin action was impaired to a similar degree in both Doc2bKO and Doc2a/Doc2bKO mice. In vitro insulin-stimulated glucose transport and GLUT4 vesicle fusion were defective in adipocytes derived from Doc2bKO mice. Surprisingly, insulin action was not altered in muscle isolated from DOC2-null mice. CONCLUSIONS/
interpretationOur study identifies a critical role for DOC2B in insulin-stimulated glucose uptake in adipocytes, and for the synergistic regulation of GSIS by DOC2A and DOC2B in beta cells.
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