Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats.
Inhibition of glucosaminyl N-deacetylase activity, a key enzyme in heparan sulphate sulphation, may be involved in the development of late diabetic vascular complications. We examined the effect of short- and long-term metabolic control on N-deacetylase activity in streptozotocin diabetic H and U rats. Spontaneously diabetic BB rats were included in parts of the study. Over a 3-week period blood glucose was maintained at predetermined levels (6-10 mmol/l or 10-20 mmol/l) by insulin treatment and then during the final 2 days rapidly reversed in half of each group. In the U rats, the hepatic N-deacetylase activity significantly decreased by 10-15% following short- and long-term poor metabolic control and the inhibition was entirely reversed by short-term good control. In the H rats a similar, not significant, effect was seen. BB rats in long-term poor control showed a 10% reduction in hepatic N-deacetylase activity (p = 0.003). Glomerular N-deacetylase activity was reduced in U rats after long-term poor control (p = 0.004) but not in H and BB rats. There was an overall correlation between urinary albumin excretion and glomerular N-deacetylase activity (r = -0.60, p < 0.0001). We conclude that diabetes-induced inhibition of hepatic N-deacetylase is not restricted to the streptozotocin diabetic model, and that short-term blood glucose control is of major importance. Genetic factors and tissue specificity influence the vulnerability of the enzyme. Finally, the study suggests an association between N-deacetylase activity and urinary albumin excretion.
Kofoed-Enevoldsen
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A
Steno Diabetes Center, Gentofte, Denmark.
Noonan
D
D
Deckert
T
T
D000419:Albuminuria; D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000235:genetics; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D007328:Insulin / Q000494:pharmacology*; D007672:Kidney Cortex / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000201:enzymology; D008099:Liver / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis
D001786:Blood Glucose; D007328:Insulin; D012333:RNA, Messenger; D000581:Amidohydrolases; C023079:N-acetylglucosamine deacetylase