Acta Pharm. 51 (2001) 85-94

Glycosaminoglycans in development and therapy of diabetic complications

DUBRAVKA JURETIC,^1* VERA KRAJNOVIC,² MARTINA ŠEPETAVC,¹  
ROBERTA PETLEVSKI ¹ and  JANA LUKAC-BAJALO³

¹Faculty of Pharmacy and Biochemistry, Department of Medical Biochemistry and Haematology, University of Zagreb, Zagreb, Croatia
²General Hospital "Dr. Josip Bencevic", Medical-biochemical laboratory, Slavonski Brod, Croatia
³Faculty of Pharmacy, Chair of Clinical Biochemistry, University of Ljubljana, Ljubljana, Slovenia

Glomerular glycosaminoglycans are the subject of increasing interest in the investigation of diabetic nephropathy because with glycoproteins heparan sulfate proteoglycan make up the polyanionic sites of the glomerular basement membrane and epithelial slit processes. They serve as the charge barrier which maintains the selective permeability of the renal filter. Defect in the regulation of heparan sulfate production by endothelial, myomedial and mesangial cells determines the susceptibility of diabetic patients to develop proteinuria. Similar changes in heparan sulfate content in the intima of the aortas of patients with diabetes mellitus have been observed, suggesting that the abnormalities in heparan sulfate metabolism are not necessarily restricted to the kidney. Numerous reports showed that heparin and, more generally, heparan sulfate or dermatan sulfate prevent and cure experimental and human diabetic nephropathy. Subcutaneous administration of these glycosaminoglycans protects peritoneal function by affecting the remodeling of the peritoneum in the patient on continuous ambulatory peritoneal dialysis. The long-term potential side-effects of glycosaminoglycan therapy are osteoporosis and bleeding.

Keywords: proteoglycans, glycosaminoglycans, heparin, heparan sulfate, dermatan sulfate, diabetic nephropathy