Inhibition of N-acetylheparosan deacetylase in diabetic rats.
The effects on N-acetylheparosan deacetylase (N-deacetylase) activity exerted by poorly and well-regulated diabetes and variation of genetic background were investigated in insulin-treated streptozocin-induced diabetic rats of two different strains (H and U). N-deacetylase plays a key role in heparan sulfate biosynthesis, because N-deacetylation is a prerequisite for N- and further O-sulfation. Specific activity of the enzyme was reduced by 50% in poorly regulated diabetic rats compared with nondiabetic rats (P less than 0.001). The decrease in specific activity was accompanied by a reduction in the estimated KM from 34 +/- 3 to 27 +/- 4 mg/L (P less than 0.001). Optimal insulin treatment, leading to near normalization of blood glucose, prevented reduction in N-deacetylase activity. In rat strain U, however, a 20% reduction was found despite optimal insulin treatment (P = 0.01), and the nondiabetic animals of this strain had reduced N-deacetylase activity compared with nondiabetic rats from the H strain. This might suggest a genetic difference between the rat strains in the regulation of the enzyme activity. The diabetes-induced inhibition of N-deacetylase may have an important role in the pathogenesis of nephropathy and vascular complications in human diabetes mellitus.
Kofoed-Enevoldsen
A
A
Steno Memorial Hospital, Gentofte, Denmark.
Eriksson
U J
UJ
D000581:Amidohydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001842:Bone and Bones / Q000002:abnormalities; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006497:Heparan Sulfate / Q000378:metabolism; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin
D000581:Amidohydrolases; D001786:Blood Glucose; D016326:Extracellular Matrix Proteins; D006497:Heparan Sulfate; D007328:Insulin; D013311:Streptozocin; C040499:N-acetylheparosan deacetylase