The function of heparanase in diabetes and its complications.
Heparan sulfate proteoglycans are ubiquitous glycoproteins that contain several heparan sulfate polysaccharide side chains attached to a core protein. They function not only as a primary structural component of the extracellular matrix, but also provide a storage depot for bioactive molecules, such as basic fibroblast growth factor, vascular endothelial growth factor and lipoprotein lipase. Heparanase is an endoglycosidase that specifically hydrolyzes heparan sulfate into oligosaccharides. Recent studies have indicated that heparanase is engaged in the initiation and progression of diabetes, in addition to its associated complications. This review focuses on the participation of heparanase in the cleavage of heparan sulfate proteoglycans in pancreatic islets promoting beta cell death, promotion of atherosclerosis, and its role in cardiac metabolic switching in the early stage of cardiomyopathy during diabetes. Understanding the mechanisms by which heparanase is regulated in diabetes could provide a drug target to prevent diabetes and its complications.
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Fang
F
Wang
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada.
Andrea
A
Wan
Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: rodrigue@mail.ubc.ca.
Brian
B
Rodrigues
D003324:Coronary Artery Disease / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000517:prevention & control*; D004847:Epithelial Cells; D005109:Extracellular Matrix; D005260:Female; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D019812:Heparan Sulfate Proteoglycans / Q000037:antagonists & inhibitors*; D006801:Humans; D008297:Male; D000099175:Heparanase
D005966:Glucuronidase; D019812:Heparan Sulfate Proteoglycans; D000099175:Heparanase
cardiomyopathie; cardiomyopathy; diabetes; diabète; heparanase; héparanase