ArticleBritish journal of pharmacology2020
Inhibition of heparanase protects against pancreatic beta cell death in streptozotocin-induced diabetic mice via reducing intra-islet inflammatory cell infiltration.
Article in British journal of pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Heparanase gene deficiency suppresses atherosclerosis progression and enhances plaque stability in apolipoprotein E gene knockout mice with diabetes.Clinical science (London, England : 1979) · 2026Article
- Article
- Association between the development of sepsis and the triglyceride-glucose index in acute pancreatitis patients: a retrospective investigation utilizing the MIMIC-IV database.BMC gastroenterology · 2025Article
- Slow Metabolism-Driven Amplification of Hepatic PPARγ Agonism Mediates Benzbromarone-Induced Obesity-Specific Liver Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sulfation pathways in the maintenance of functional beta-cell mass and implications for diabetes.Essays in biochemistry · 2024Review
- Article
- First GPR119 PET Imaging Ligand: Synthesis, Radiochemistry, and Preliminary Evaluations.Journal of medicinal chemistry · 2023Article
- Importance of Heparan Sulfate Proteoglycans in Pancreatic Islets and β-Cells.International journal of molecular sciences · 2022Review
- Unfractionated Heparin Attenuated Histone-Induced Pulmonary Syndecan-1 Degradation in Mice: a Preliminary Study on the Roles of Heparinase Pathway.Inflammation · 2022Article
- Identification of Heparan Sulfate in Dilated Cardiomyopathy by Integrated Bioinformatics Analysis.Frontiers in cardiovascular medicine · 2022Article
- Integrative biology of extracellular vesicles in diabetes mellitus and diabetic complications.Theranostics · 2022Review
- Dichotomic role of heparanase in a murine model of metabolic syndrome.Cellular and molecular life sciences : CMLS · 2021Article
- Inhibition of heparanase protects against pancreatic beta cell death in streptozotocin-induced diabetic mice via reducing intra-islet inflammatory cell infiltration.British journal of pharmacology · 2020Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
background and purposeIntra-islet heparan sulfate (HS) plays an important role in the maintenance of pancreatic islet function. The aim of this study was to investigate the effect mechanism of HS loss on the functioning of islets in diabetic mice. EXPERIMENTAL APPROACH: The hypoglycaemic effect of a heparanase inhibitor, OGT2115, was tested in a streptozotocin-induced diabetic mouse model. The islets in pancreatic sections were also stained to reveal their morphology. An insulinoma cell line (MIN6) and primary isolated murine islets were used to investigate the effect of OGT2115 in vitro. KEY
resultsIntra-islet HS was clearly lost in streptozotocin-induced diabetic mice due to the increased heparanase expression in damaged islets. OGT2115 prevented intra-islet HS loss and improved the glucose profile and insulin secretion in streptozotocin-treated mice. The apoptosis of pancreatic beta cells and the infiltration of mononuclear macrophages, CD4- and CD8-positive T-cells in islets was reduced by OGT2115 in streptozotocin-treated mice, but OGT2115 did not alter the direct streptozotocin-induced damage in vitro. The expression of heparanase was increased in high glucose-treated isolated islets but not in response to direct streptozotocin stimulation. Further experiments showed that high glucose stimuli could decreased expression of PPARγ in cultured islets, thereby relieving the PPARγ-induced inhibition of heparanase gene expression. CONCLUSION AND IMPLICATIONS: Hyperglycaemia could cause intra-islet HS loss by elevating the expression of heparanase, thereby aggravating inflammatory cell infiltration and islet damage. Inhibition of heparanase might provide benefit for pancreatic beta cell protection in Type 1 diabetes.
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