{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Loka RS"],"funding":["National Institute of Diabetes and Digestive and Kidney Diseases","NIDDK NIH HHS","National Institute of General Medical Sciences","NIGMS NIH HHS"],"pagination":["1387-1400"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9251817"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(6)"],"pubmed_abstract":["Diabetes is a chronic disease in which the levels of blood glucose are too high because the body does not effectively produce insulin to meet its needs or is resistant to insulin. β Cells in human pancreatic islets produce insulin, which signals glucogen production by the liver and causes muscles and fat to uptake glucose. Progressive loss of insulin-producing β cells is the main cause of both type 1 and type 2 diabetes. Heparan sulfate (HS) is a ubiquitous polysaccharide found at the cell surface and in the extracellular matrix (ECM) of a variety of tissues. HS binds to and assembles proteins in ECM, thus playing important roles in the integrity of ECM (particularly basement membrane), barrier function, and ECM-cell interactions. Islet HS is highly expressed by the pancreatic β cells and critical for the survival of β cells. Heparanase is an endoglycosidase and cleaves islet HS in the pancreas, resulting in β-cell death and oxidative stress. Heparanase could also accelerate β-cell death by promoting cytokine release from ECM and secretion by activated inflammatory and endothelial cells. We demonstrate that HS-mimicking glycopolymer, a potent heparanase inhibitor, improves the survival of cultured mouse pancreatic β cells and protects HS contents under the challenge of heparanase in human pancreatic islets. Moreover, this HS-mimicking glycopolymer reduces the expression levels of cytokines (IL8, IL1β, and TNFα) and the gene encoding Toll-like Receptor 2 (TLR2) in human pancreatic islets."],"journal":["ACS chemical biology"],"pubmed_title":["Heparan Sulfate Mimicking Glycopolymer Prevents Pancreatic β Cell Destruction and Suppresses Inflammatory Cytokine Expression in Islets under the Challenge of Upregulated Heparanase."],"pmcid":["PMC9251817"],"funding_grant_id":["R01 DK090313","R01 GM098285"],"pubmed_authors":["Sletten ET","Zhang K","Kayal Y","Nguyen HM","Vlodavsky I","Loka RS","Song Z"],"additional_accession":[]},"is_claimable":false,"name":"Heparan Sulfate Mimicking Glycopolymer Prevents Pancreatic β Cell Destruction and Suppresses Inflammatory Cytokine Expression in Islets under the Challenge of Upregulated Heparanase.","description":"Diabetes is a chronic disease in which the levels of blood glucose are too high because the body does not effectively produce insulin to meet its needs or is resistant to insulin. β Cells in human pancreatic islets produce insulin, which signals glucogen production by the liver and causes muscles and fat to uptake glucose. Progressive loss of insulin-producing β cells is the main cause of both type 1 and type 2 diabetes. Heparan sulfate (HS) is a ubiquitous polysaccharide found at the cell surface and in the extracellular matrix (ECM) of a variety of tissues. HS binds to and assembles proteins in ECM, thus playing important roles in the integrity of ECM (particularly basement membrane), barrier function, and ECM-cell interactions. Islet HS is highly expressed by the pancreatic β cells and critical for the survival of β cells. Heparanase is an endoglycosidase and cleaves islet HS in the pancreas, resulting in β-cell death and oxidative stress. Heparanase could also accelerate β-cell death by promoting cytokine release from ECM and secretion by activated inflammatory and endothelial cells. We demonstrate that HS-mimicking glycopolymer, a potent heparanase inhibitor, improves the survival of cultured mouse pancreatic β cells and protects HS contents under the challenge of heparanase in human pancreatic islets. Moreover, this HS-mimicking glycopolymer reduces the expression levels of cytokines (IL8, IL1β, and TNFα) and the gene encoding Toll-like Receptor 2 (TLR2) in human pancreatic islets.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jun","modification":"2024-11-19T16:53:30.387Z","creation":"2022-07-22T07:06:24.001Z"},"accession":"S-EPMC9251817","cross_references":{"pubmed":["35658404"],"doi":["10.1021/acschembio.1c00908"]}}