Inhibition of glomerular glucosaminyl N-deacetylase in diabetic rats.
The enzyme glucosaminyl N-deacetylase plays a key role in heparan sulphate biosynthesis since N-deacetylation is a prerequisite for N- and further O-sulphation of the carbohydrate polymer. Diabetes induced inhibition of this enzyme could be an important factor in the development of diabetic nephropathy. In this study glomerular glucosaminyl N-deacetylase activity and urinary albumin excretion were measured in insulin-treated streptozotocin-diabetic rats. Furthermore, in an attempt to provide evidence of genetically dependent differences in the vulnerability of the N-deacetylase enzyme, two closely related rat strains (H and U) were studied. A significant 10% inhibition in enzyme activity was found among rats with mean blood glucose values between 9 and 17 mmol/liter, P less than 0.05. There was a pronounced difference between the two rat strains in the vulnerability of the enzyme against blood glucose alterations. The U rat appeared highly sensitive to short-term blood glucose control judged by the correlation between blood glucose and N-deacetylase activity (r = -0.73, P = 0.005, N = 16), where no such correlation was found in the H rat (r = 0.02, P = 0.9, N = 14). Urinary albumin excretion was increased in diabetic H rats and significantly correlated to glomerular N-deacetylase activity (r = -0.62, P = 0.02, N = 14). The U rats developed a 10-fold rise in albumin excretion compared to H rats, but this albuminuria was apparently not related to the presence of diabetes or correlated to glomerular N-deacetylase activity. It is concluded that the diabetes induced inhibition of glucosaminyl N-deacetylase may play an important role in the pathogenesis of diabetic nephropathy.
Kofoed-Enevoldsen
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Steno Diabetes Centre, Gentofte, Denmark.
D000419:Albuminuria / Q000209:etiology; D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000201:enzymology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D000581:Amidohydrolases; C023079:N-acetylglucosamine deacetylase