Inhibition of N-acetylheparosan deacetylase in diabetic rats.

Abstract:

: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.

journal_name

Diabetes

journal_title

Diabetes

authors

Kofoed-Enevoldsen A,Eriksson UJ

doi

10.2337/diab.40.11.1449

subject

Has Abstract

pub_date

1991-11-01 00:00:00

pages

1449-52

issue

11

eissn

0012-1797

issn

1939-327X

journal_volume

40

pub_type

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