ArticleNature communications2022
The IGFBP3/TMEM219 pathway regulates beta cell homeostasis.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Effect of Verapamil on Blood Glucose in Type 1 and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.Cardiovascular drugs and therapy · 2026Pooled it
- Integrated single-cell and metabolomic profiling identifies ovarian metabolic differences and endothelial heterogeneity associated with litter-size variation in Hu sheep.Journal of animal science and biotechnology · 2026Article
- 4-Methylumbelliferone for type 1 diabetes therapy: evidence for β-cell protection via EGFR/PI3K/Akt signaling.Journal of endocrinological investigation · 2026Article
- Insulin-like growth factor receptor signaling in physiology and disease.Signal transduction and targeted therapy · 2026Review
- IGFBP-3 enhances irinotecan efficacy in colorectal cancerResearch in pharmaceutical sciences · 2026Article
- Higher osteocalcin levels are associated with preserved β-cell function in early-established type 1 diabetes.Journal of endocrinological investigation · 2026Article
- Review
- Synergistic cytotoxicity of recombinant IGFBP-3 and cisplatin in HPV18-positive HeLa cellsResearch in pharmaceutical sciences · 2026Article
- POLK and KCNK17 as novel candidate genes for type 2 diabetes via stress response and ion channel regulation.Journal of endocrinological investigation · 2026Article
- Review
- Mitochondria-associated programmed cell death in pancreatic β cell of T2DM.Apoptosis : an international journal on programmed cell death · 2026Review
- Branched-chain α-keto acids impair glucose-stimulated insulin secretion in pancreatic β-cells under diabetes by reactivating the LDHA-lactate axis.Nature communications · 2026Article
- Dissecting the shared genetic landscape of schizophrenia and hippocampal subfields: A genome-wide cross-trait analysis.Translational psychiatry · 2026Article
- The role of the incretin GIP in inflammation.Journal of endocrinological investigation · 2026Review
- Endothelial Cell Heterogeneity in Carotid Plaque Calcification: An Exploratory Single-Cell Transcriptomic Study with Proteomic Support.International journal of general medicine · 2026Article
- Identification and dual-center histological validation of EMT core genes in chronic rhinosinusitis with nasal polyps: an integrated multi-cohort transcriptomic and single-cell analysis.Frontiers in immunology · 2026Article
- Insulin-like growth factor (IGF) and Insulin-like growth factor binding proteins (IGFBP) as predictors of type 2 diabetes risk in obese adults.Journal of diabetes and metabolic disorders · 2025Article
- Unveiling the role of the extracellular matrix in the osteosarcoma tumor microenvironment through integrated transcriptomics and experimental validation.Cancer gene therapy · 2025Article
- Epigen-mediated mechanisms to alleviate glucose homeostasis disruptions in diet-induced obese and STZ-induced diabetic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- A multifaceted investigation into the impact of m6A methylation-related genes on pancreatic cancer, integrating insights from various databases and foundational experimental research.Annals of medicine and surgery (2012) · 2025Article
Corrections and comments
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Authors and funding
30 authors at 15 institutions in 6 countries.
Funding
Abstract
Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients' cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
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