To date three different forms of N-deacetylase/N-sulfotransferase have been cloned [37,38]. The activity of N-deacetylase/N-sulfotransferase is approximately 40% lower in hepatocytes from streptozotocin diabetic rats as compared with control cells . Furthermore, Kofoed-Enevoldsen et al  found a reduction in N-deacetylase/N-sulfotransferase activity in streptozotocin diabetic rats. In humans, the activity or gene expression of N-deacetylase/N-sulfotransferase has been evaluated in cell cultures of skin fibroblasts obtained from diabetic patients with/without diabetic nephropathy. Neither the activity of N-deacetylase/N-sulfotransferase in type 1 diabetics  nor mRNA levels of N-deacetylase/N-sulfotransferase 1 and 2, in type 2 diabetic patients  levels were altered. Interestingly, only the N-deacetylase/N-sulfotransferase 2 gene expression was down-regulated by diabetes, but this was only in skin fibroblasts, not in mesangial cells .
It should be recognized that N-deacetylase/N-sulfotransferase 1 and 2 enzymes are not the only enzymes involved in HS-PG sulfation. Indeed, N-deacetylase/N-sulfotransferase 3, epimerase and the 3-O-sulfotransferases may also substantially contribute to HS-PG sulfation. Interestingly, while there is no data in the literature on the effect of the diabetic milieu on the activity of the two former, quite recently Edge and Spiro  have obtained findings suggesting an abnormal activity of isoforms of 3-O-sulfotransferase. Indeed, a highly specific reduction in the disaccharide unit IdUA(2S)a1^4GlcN(3S) was observed in the GBM from kidneys of patients (not reported whether type 1 or 2 diabetics) with diabetic nephropathy. This disaccharide unit has so far been found only in the HS from GBM in substantial quantities representing approximately 20% of all HS disaccharide units.
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