ArticleThe Journal of biological chemistry2014
Thioredoxin-interacting protein promotes islet amyloid polypeptide expression through miR-124a and FoxA2.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Caveolin-1 Modulates Islet Amyloid Polypeptide Expression Through Interaction with TXNIP in Murine Pancreatic β-Cells.Biomedicines · 2026Article
- New horizon of the combined BCG vaccine with probiotic and liraglutide in augmenting beta cell survivalHeliyon · 2024Article
- UTRs and Ago-2/miR-335 Complex Restricts Amylin Translation in Insulinoma and Human Pancreatic β-Cells.International journal of molecular sciences · 2024Article
- The role of TXNIP in cancer: a fine balance between redox, metabolic, and immunological tumor control.British journal of cancer · 2023Review
- miR-124 is upregulated in diabetic mice and inhibits proliferation and promotes apoptosis of high-glucose-induced β-cells by targeting EZH2.World journal of diabetes · 2023Article
- A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis.Theranostics · 2023Article
- Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis.Endocrinology · 2022Review
- Arc Regulates Transcription of Genes for Plasticity, Excitability and Alzheimer's Disease.Biomedicines · 2022Article
- TXNIP inhibition in the treatment of diabetes. Verapamil as a novel therapeutic modality in diabetic patients.Medicine and pharmacy reports · 2022Review
- Thioredoxin-Interacting Protein in Cancer and Diabetes.Antioxidants & redox signaling · 2022Review
- Molecular Mechanisms of Amylin Turnover, Misfolding and Toxicity in the Pancreas.Molecules (Basel, Switzerland) · 2022Review
- Redox Homeostasis in Pancreatic β-Cells: From Development to Failure.Antioxidants (Basel, Switzerland) · 2021Review
- FoxA2 and RNA Pol II mediate human islet amyloid polypeptide turnover in ER-stressed pancreatic β-cells.The Biochemical journal · 2021Article
- TXNIP/TBP-2: A Master Regulator for Glucose Homeostasis.Antioxidants (Basel, Switzerland) · 2020Review
- Thioredoxin, thioredoxin interacting protein and transducer and activator of transcription 3 in gestational diabetes.Molecular biology reports · 2020Article
- Epigenetic repression of miR-17 contributed to di(2-ethylhexyl) phthalate-triggered insulin resistance by targeting Keap1-Nrf2/miR-200a axis in skeletal muscle.Theranostics · 2020Article
- microRNA-690 regulates induced pluripotent stem cells (iPSCs) differentiation into insulin-producing cells by targeting Sox9.Stem cell research & therapy · 2019Article
- Thioredoxin-Interacting Protein (TXNIP) Associated NLRP3 Inflammasome Activation in Human Alzheimer's Disease Brain.Journal of Alzheimer's disease : JAD · 2019Article
- Functional proteasome complex is required for turnover of islet amyloid polypeptide in pancreatic β-cells.The Journal of biological chemistry · 2018Article
- Diabetes pathogenic mechanisms and potential new therapies based upon a novel target called TXNIP.Current opinion in endocrinology, diabetes, and obesity · 2018Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Thioredoxin-interacting protein (TXNIP) is up-regulated by glucose and diabetes and plays a critical role in glucotoxicity, inflammation, and beta-cell apoptosis, whereas we have found that TXNIP deficiency protects against diabetes. Interestingly, human islet amyloid polypeptide (IAPP) is also induced by glucose, aggregates into insoluble amyloid fibrils found in islets of most individuals with type 2 diabetes and promotes inflammation and beta-cell cytotoxicity. However, so far no connection between TXNIP and IAPP signaling had been reported. Using TXNIP gain and loss of function experiments, INS-1 beta-cells and beta-cell-specific Txnip knock-out mice, we now found that TXNIP regulates IAPP expression. Promoter analyses and chromatin-immunoprecipitation assays further demonstrated that TXNIP increases IAPP expression at the transcriptional level, and we discovered that TXNIP-induced FoxA2 (forkhead box A2) transcription factor expression was conferring this effect by promoting FoxA2 enrichment at the proximal FoxA2 site in the IAPP promoter. Moreover, we found that TXNIP down-regulates miR-124a expression, a microRNA known to directly target FoxA2. Indeed, miR-124a overexpression led to decreased FoxA2 expression and IAPP promoter occupancy and to a significant reduction in IAPP mRNA and protein expression and also effectively inhibited TXNIP-induced IAPP expression. Thus, our studies have identified a novel TXNIP/miR-124a/FoxA2/IAPP signaling cascade linking the critical beta-cell signaling pathways of TXNIP and IAPP and thereby provide new mechanistic insight into an important aspect of transcriptional regulation and beta-cell biology.
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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.