ArticleThe Journal of clinical investigation2014
SORCS1 is necessary for normal insulin secretory granule biogenesis in metabolically stressed β cells.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Finding memo: versatile interactions of the VPS10p-Domain receptors in Alzheimer's disease.Molecular neurodegeneration · 2022Pooled it
- Human Islet miR-199a-5p and miR-214-3p Associate With Donor Age, BMI, and Sex and Mediate Cellular Aging in Islet-Derived Cells.Acta physiologica (Oxford, England) · 2026Article
- Genetics and diet shape the relationship between islet function and whole body metabolism.American journal of physiology. Endocrinology and metabolism · 2024Article
- SORCS2 activity in pancreatic α-cells safeguards insulin granule formation and release from glucose-stressed β-cells.iScience · 2024Article
- Article
- Review
- Emerging roles of sortilin in affecting the metabolism of glucose and lipid profiles.Bosnian journal of basic medical sciences · 2022Review
- XBP1 maintains beta cell identity, represses beta-to-alpha cell transdifferentiation and protects against diabetic beta cell failure during metabolic stress in mice.Diabetologia · 2022Article
- The Tetracycline-Controlled Transactivator (Tet-On/Off) System in β-Cells Reduces Insulin Expression and Secretion in Mice.Diabetes · 2021Article
- In pancreatic β-cells myosin 1b regulates glucose-stimulated insulin secretion by modulating an early step in insulin granule trafficking from the Golgi.Molecular biology of the cell · 2021Article
- 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
- A fluorescent timer reporter enables sorting of insulin secretory granules by age.The Journal of biological chemistry · 2020Article
- Genomic inbreeding trends, influential sire lines and selection in the global Thoroughbred horse population.Scientific reports · 2020Article
- Type 2 diabetes-associated single nucleotide polymorphism in Sorcs1 gene results in alternative processing of the Sorcs1 protein in INS1 β-cells.Scientific reports · 2019Article
- Article
- Mutant Huntingtin Affects Diabetes and Alzheimer's Markers in Human and Cell Models of Huntington's Disease.Cells · 2019Article
- Lysosomal degradation of newly formed insulin granules contributes to β cell failure in diabetes.Nature communications · 2019Article
- Reduced uterine perfusion pressure causes loss of pancreatic β-cell area but normal function in fetal rat offspring.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Vti1a/b regulate synaptic vesicle and dense core vesicle secretion via protein sorting at the Golgi.Nature communications · 2018Article
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 2 countries.
Funding
Abstract
We previously positionally cloned Sorcs1 as a diabetes quantitative trait locus. Sorcs1 belongs to the Vacuolar protein sorting-10 (Vps10) gene family. In yeast, Vps10 transports enzymes from the trans-Golgi network (TGN) to the vacuole. Whole-body Sorcs1 KO mice, when made obese with the leptin(ob) mutation (ob/ob), developed diabetes. β Cells from these mice had a severe deficiency of secretory granules (SGs) and insulin. Interestingly, a single secretagogue challenge failed to consistently elicit an insulin secretory dysfunction. However, multiple challenges of the Sorcs1 KO ob/ob islets consistently revealed an insulin secretion defect. The luminal domain of SORCS1 (Lum-Sorcs1), when expressed in a β cell line, acted as a dominant-negative, leading to SG and insulin deficiency. Using syncollin-dsRed5TIMER adenovirus, we found that the loss of Sorcs1 function greatly impairs the rapid replenishment of SGs following secretagogue challenge. Chronic exposure of islets from lean Sorcs1 KO mice to high glucose and palmitate depleted insulin content and evoked an insulin secretion defect. Thus, in metabolically stressed mice, Sorcs1 is important for SG replenishment, and under chronic challenge by insulin secretagogues, loss of Sorcs1 leads to diabetes. Overexpression of full-length SORCS1 led to a 2-fold increase in SG content, suggesting that SORCS1 is sufficient to promote SG biogenesis.
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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.