Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin

<p>Abstract</p> <p>Background</p> <p>Heparan sulfate proteoglycans (HSPGs) contain glycosaminoglycan (GAG) chains made primarily of heparan sulfate (HS). Hyperglycemia in diabetes leads to endothelial injury and nephropathy, retinopathy and atherosclerosis. Decreased HS...

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Main Authors: Linhardt Robert J, Xie Jin, Zhang Fuming, Han Juying, Hiebert Linda M
Format: Article
Language:English
Published: BMC 2009-08-01
Series:Cardiovascular Diabetology
Online Access:http://www.cardiab.com/content/8/1/46
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author Linhardt Robert J
Xie Jin
Zhang Fuming
Han Juying
Hiebert Linda M
author_facet Linhardt Robert J
Xie Jin
Zhang Fuming
Han Juying
Hiebert Linda M
author_sort Linhardt Robert J
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Heparan sulfate proteoglycans (HSPGs) contain glycosaminoglycan (GAG) chains made primarily of heparan sulfate (HS). Hyperglycemia in diabetes leads to endothelial injury and nephropathy, retinopathy and atherosclerosis. Decreased HSPG may contribute to diabetic endothelial injury. Decreased tissue HS in diabetes has been reported, however, endothelial HS changes are poorly studied.</p> <p>Objective</p> <p>To determine total GAGs, including HS, in endothelium under hyperglycemic conditions and the protective effect of insulin and heparin.</p> <p>Methods</p> <p>Confluent primary porcine aortic endothelial cells (PAECs) were divided into control, glucose (30 mM), insulin (0.01 unit/ml) and glucose plus insulin treatment groups for 24, 48 and 72 hours. Additionally, PAECs were treated with glucose, heparin (0.5 <it>μ</it>g/ml) and glucose plus heparin for 72 hours. GAGs were isolated from cells and medium. GAG concentrations were determined by the carbazole assay and agarose gel electrophoresis.</p> <p>Results</p> <p>GAGs were significantly increased only in control and glucose plus insulin groups at 72 versus 24 hours. Glucose decreased cell GAGs and increased medium GAGs, and insulin alone decreased cell GAGs at all times compared to control. In the glucose plus insulin group, cell GAGs were less than control at 24 hours, and greater than glucose or insulin alone at 48 and 72 hours while GAGs in medium were greater than control at all times and glucose at 72 hours. Heparin increased GAGs in glucose treated cells and medium.</p> <p>Conclusion</p> <p>High glucose and insulin alone reduces endothelial GAGs. In hyperglycemic conditions, heparin or insulin preserves GAGs which may protect cells from injury. Insulin is an effective diabetic therapy since it not only lowers blood glucose, but also protects endothelium.</p>
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spelling doaj.art-ca553fac724f45c58e76e5f4470e9eef2022-12-22T03:10:14ZengBMCCardiovascular Diabetology1475-28402009-08-01814610.1186/1475-2840-8-46Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparinLinhardt Robert JXie JinZhang FumingHan JuyingHiebert Linda M<p>Abstract</p> <p>Background</p> <p>Heparan sulfate proteoglycans (HSPGs) contain glycosaminoglycan (GAG) chains made primarily of heparan sulfate (HS). Hyperglycemia in diabetes leads to endothelial injury and nephropathy, retinopathy and atherosclerosis. Decreased HSPG may contribute to diabetic endothelial injury. Decreased tissue HS in diabetes has been reported, however, endothelial HS changes are poorly studied.</p> <p>Objective</p> <p>To determine total GAGs, including HS, in endothelium under hyperglycemic conditions and the protective effect of insulin and heparin.</p> <p>Methods</p> <p>Confluent primary porcine aortic endothelial cells (PAECs) were divided into control, glucose (30 mM), insulin (0.01 unit/ml) and glucose plus insulin treatment groups for 24, 48 and 72 hours. Additionally, PAECs were treated with glucose, heparin (0.5 <it>μ</it>g/ml) and glucose plus heparin for 72 hours. GAGs were isolated from cells and medium. GAG concentrations were determined by the carbazole assay and agarose gel electrophoresis.</p> <p>Results</p> <p>GAGs were significantly increased only in control and glucose plus insulin groups at 72 versus 24 hours. Glucose decreased cell GAGs and increased medium GAGs, and insulin alone decreased cell GAGs at all times compared to control. In the glucose plus insulin group, cell GAGs were less than control at 24 hours, and greater than glucose or insulin alone at 48 and 72 hours while GAGs in medium were greater than control at all times and glucose at 72 hours. Heparin increased GAGs in glucose treated cells and medium.</p> <p>Conclusion</p> <p>High glucose and insulin alone reduces endothelial GAGs. In hyperglycemic conditions, heparin or insulin preserves GAGs which may protect cells from injury. Insulin is an effective diabetic therapy since it not only lowers blood glucose, but also protects endothelium.</p>http://www.cardiab.com/content/8/1/46
spellingShingle Linhardt Robert J
Xie Jin
Zhang Fuming
Han Juying
Hiebert Linda M
Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
Cardiovascular Diabetology
title Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
title_full Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
title_fullStr Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
title_full_unstemmed Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
title_short Changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
title_sort changes in cultured endothelial cell glycosaminoglycans under hyperglycemic conditions and the effect of insulin and heparin
url http://www.cardiab.com/content/8/1/46
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AT zhangfuming changesinculturedendothelialcellglycosaminoglycansunderhyperglycemicconditionsandtheeffectofinsulinandheparin
AT hanjuying changesinculturedendothelialcellglycosaminoglycansunderhyperglycemicconditionsandtheeffectofinsulinandheparin
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