ArticlePLoS genetics2011
Positional cloning of a type 2 diabetes quantitative trait locus; tomosyn-2, a negative regulator of insulin secretion.
Article in PLoS genetics, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Optimizing diabetic kidney disease animal models: Insights from a meta-analytic approach.Animal models and experimental medicine · 2023Pooled it
- CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Tomosyn-2 Regulates Postnatal β-Cell Expansion and Insulin Secretion to Maintain Glucose Homeostasis.Diabetes · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
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- Review
- Z-flipon variants reveal the many roles of Z-DNA and Z-RNA in health and disease.Life science alliance · 2023Article
- Analysis of a genetic region affecting mouse body weight.Physiological genomics · 2023Article
- Regulation of insulin secretion by the post-translational modifications.Frontiers in cell and developmental biology · 2023Review
- The chromosome-scale genome of the raccoon dog: Insights into its evolutionary characteristics.iScience · 2022Article
- β Cell-specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses.JCI insight · 2022Article
- Meta-Inflammation and De Novo Lipogenesis Markers Are Involved in Metabolic Associated Fatty Liver Disease Progression in BTBR ob/ob Mice.International journal of molecular sciences · 2022Article
- Prostaglandin EP3 receptor signaling is required to prevent insulin hypersecretion and metabolic dysfunction in a non-obese mouse model of insulin resistance.American journal of physiology. Endocrinology and metabolism · 2021Article
- Rat prostaglandin EP3 receptor is highly promiscuous and is the sole prostanoid receptor family member that regulates INS-1 (832/3) cell glucose-stimulated insulin secretion.Pharmacology research & perspectives · 2021Article
- Insulin granule biogenesis and exocytosis.Cellular and molecular life sciences : CMLS · 2021Review
- Genetic evidence for an inhibitory role of tomosyn in insulin-stimulated GLUT4 exocytosis.Traffic (Copenhagen, Denmark) · 2020Article
- Recent Insights into Beta-cell Exocytosis in Type 2 Diabetes.Journal of molecular biology · 2020Review
- Gene loci associated with insulin secretion in islets from non-diabetic mice.The Journal of clinical investigation · 2019Article
- A gene expression network analysis of the pancreatic islets from lean and obese mice identifies complement 1q like-3 secreted protein as a regulator of β-cell function.Scientific reports · 2019Article
- Complement 1q-like-3 protein inhibits insulin secretion from pancreatic β-cells via the cell adhesion G protein-coupled receptor BAI3.The Journal of biological chemistry · 2018Article
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
We previously mapped a type 2 diabetes (T2D) locus on chromosome 16 (Chr 16) in an F2 intercross from the BTBR T (+) tf (BTBR) Lep(ob/ob) and C57BL/6 (B6) Lep(ob/ob) mouse strains. Introgression of BTBR Chr 16 into B6 mice resulted in a consomic mouse with reduced fasting plasma insulin and elevated glucose levels. We derived a panel of sub-congenic mice and narrowed the diabetes susceptibility locus to a 1.6 Mb region. Introgression of this 1.6 Mb fragment of the BTBR Chr 16 into lean B6 mice (B6.16(BT36-38)) replicated the phenotypes of the consomic mice. Pancreatic islets from the B6.16(BT36-38) mice were defective in the second phase of the insulin secretion, suggesting that the 1.6 Mb region encodes a regulator of insulin secretion. Within this region, syntaxin-binding protein 5-like (Stxbp5l) or tomosyn-2 was the only gene with an expression difference and a non-synonymous coding single nucleotide polymorphism (SNP) between the B6 and BTBR alleles. Overexpression of the b-tomosyn-2 isoform in the pancreatic β-cell line, INS1 (832/13), resulted in an inhibition of insulin secretion in response to 3 mM 8-bromo cAMP at 7 mM glucose. In vitro binding experiments showed that tomosyn-2 binds recombinant syntaxin-1A and syntaxin-4, key proteins that are involved in insulin secretion via formation of the SNARE complex. The B6 form of tomosyn-2 is more susceptible to proteasomal degradation than the BTBR form, establishing a functional role for the coding SNP in tomosyn-2. We conclude that tomosyn-2 is the major gene responsible for the T2D Chr 16 quantitative trait locus (QTL) we mapped in our mouse cross. Our findings suggest that tomosyn-2 is a key negative regulator of insulin secretion.
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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.