ArticleThe Journal of clinical investigation2012
Heparan sulfate and heparanase play key roles in mouse β cell survival and autoimmune diabetes.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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Who cites it
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 166 citations in OpenAlex.
- A Genome-Wide Association Study of Prediabetes Status Change.Frontiers in endocrinology · 2022Pooled it
- Heparanase gene deficiency suppresses atherosclerosis progression and enhances plaque stability in apolipoprotein E gene knockout mice with diabetes.Clinical science (London, England : 1979) · 2026Article
- Sensing and Communicating β-Cell Stress in the Context of T1D Etiology: New Opportunities for Therapeutic Impact.Comprehensive Physiology · 2026Review
- Synthesis, Structure, and Function of Heparan Sulfate Glycopolymers to Investigate Glycosaminoglycan-Protein Interactions.Accounts of chemical research · 2026Article
- Vascular Destabilization and Pericyte Detachment are Mediated by hIAPP Aggregation in Transgenic Mice.bioRxiv : the preprint server for biology · 2026Article
- Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target.Frontiers in immunology · 2026Review
- Transient Inflammation of Pancreatic Exocrine Tissue in Autoimmune Diabetes Follows Onset of Islet Damage and Utilizes Heparanase-1.International journal of molecular sciences · 2025Article
- The matricellular protein Fibulin-5 regulates β-cell proliferation in an autocrine/paracrine manner.iScience · 2025Article
- State of the Art of Bioengineering Approaches in Beta-Cell Replacement.Current transplantation reports · 2025Review
- Stressed β-cells contribute to loss of peri-islet extracellular matrix in type 1 diabetes.Frontiers in endocrinology · 2025Article
- Sulfation pathways in the maintenance of functional beta-cell mass and implications for diabetes.Essays in biochemistry · 2024Review
- Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- The novel HS-mimetic, Tet-29, regulates immune cell trafficking across barriers of the CNS during inflammation.Journal of neuroinflammation · 2023Article
- The pathogenic "symphony" in type 1 diabetes: A disorder of the immune system, β cells, and exocrine pancreas.Cell metabolism · 2023Review
- Heparanase 2 (Hpa2)- a new player essential for pancreatic acinar cell differentiation.Cell death & disease · 2023Article
- Heparanase-A single protein with multiple enzymatic and nonenzymatic functions.Proteoglycan research · 2023Review
- Three-dimensional bioprinting of functional β-islet-like constructs.International journal of bioprinting · 2023Article
- A Universal and Modular Scaffold for Heparanase Activatable Probes and Drugs.Bioconjugate chemistry · 2022Article
- Review
- Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The autoimmune type 1 diabetes (T1D) that arises spontaneously in NOD mice is considered to be a model of T1D in humans. It is characterized by the invasion of pancreatic islets by mononuclear cells (MNCs), which ultimately leads to destruction of insulin-producing β cells. Although T cell dependent, the molecular mechanisms triggering β cell death have not been fully elucidated. Here, we report that a glycosaminoglycan, heparan sulfate (HS), is expressed at extraordinarily high levels within mouse islets and is essential for β cell survival. In vitro, β cells rapidly lost their HS and died. β Cell death was prevented by HS replacement, a treatment that also rendered the β cells resistant to damage from ROS. In vivo, autoimmune destruction of islets in NOD mice was associated with production of catalytically active heparanase, an HS-degrading enzyme, by islet-infiltrating MNCs and loss of islet HS. Furthermore, in vivo treatment with the heparanase inhibitor PI-88 preserved intraislet HS and protected NOD mice from T1D. Our results identified HS as a critical molecular requirement for islet β cell survival and HS degradation as a mechanism for β cell destruction. Our findings suggest that preservation of islet HS could be a therapeutic strategy for preventing T1D.
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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.