Summary
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.
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Klein DJ, Oegema TR, Brown DM (1989) Release of glomerular heparan-35SO4 proteoglycan by heparin from glomeruli of streptozocin-induced diabetic rats. Diabetes 38: 130–139
Kanwar YS, Rosenzweig LJ, Linker A, Jakubowski ML (1983) Decreased de novo synthesis of glomerular proteoglycans in diabetes. Proc Natl Acad Sci USA 80: 2272–2275
Wu V-Y, Wilson B, Cohen MP (1987) Disturbances in glomerular basement membrane glycosaminoglycans in experimental diabetes. Diabetes 36: 679–683
Deckert T, Feldt-Rasmussen B, Borch-Johnsen K, Jensen T, Kofoed-Enevoldsen A (1989) Albuminuria reflects widespread vascular damage. The Steno hypothesis. Diabetologia 32: 219–226
Kofoed-Enevoldsen A, Eriksson UJ (1991) Inhibition of N-acetylheparosan deacetylase in diabetic rats. Diabetes 40: 1449–1452
Unger E, Pettersson I, Eriksson UJ, Lindahl U, Kjellén L (1991) Decreased activity of the heparan sulfate modifying enzyme glucosaminyl N-deacatylase in hepatocytes from streptozotocin-diabetic rats. J Biol Chem 266: 8671–8674
Kofoed-Enevoldsen A (1992) Inhibition of glomerular glucosaminyl N-deacetylase in diabetic rats. Kidney Int 41: 763–767
Kjellén L, Bielefeld D, Höök M (1983) Reduced sulfatation of liver heparan sulfate in experimentally diabetic rats. Diabetes 32: 337–342
Kanwar YS, Linker A, Farquhar MG (1980) Increased permeability of the glomerular basement membrane to ferritin after removal of glycosaminoglycans (heparan sulfate) by enzyme digestion. J Cell Biol 86: 688–693
Castellot J, Hoover RL, Harper PA, Karnovsky MJ (1985) Heparin and glomerular epithelial cell-secreted heparin like species inhibit mesangial cell proliferation. Am J Pathol 120: 427–435
van den Born J, van den Heuvel LPWJ, Bakker MAH, Veerkamp JH, Assmann KJM, Berden JHM (1992) A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. Kidney Int 41: 115–123
Remuzzi G, Bertani T (1990) Is glomerulosclerosis a consequence of altered glomerular permeability to macromolecules. Kidney Int 38: 384–394
Ofuso FA, Modi J, Blajchman MA, Buchanan MR, Johnson EA (1987) Increased sulphation improves the anticoagulant activities of heparan sulphate and dermatan sulphate. Biochem J 248: 889–896
Cifonelli JA (1974) The relationship of molecular weight, and sulfate content and distribution to anticoagulant activity of heparin preparations. Carbohydrate Res 37: 145–154
Brown D, Steffes MW, Thibert P, Azar S, Mauer SM (1983) Glomerular manifestations of diabetes in the BB rat. Metabolism 32 [Suppl 1]: 131–135
Eriksson UJ (1988) Importance of genetic predisposition and maternal environment for the occurrence of congenital malformations in offspring of diabetic rats. Teratology 137: 365–374
Markholst H, Eastman S, Wilson D, Andreasen BE, Lernmark Å (1991) Diabetes segregates as a single locus in crosses between inbred BB rats prone or resistant. J Exp Med 174: 297–300
Navia JL, Riesenfeld J, Vann WF, Lindahl U, Rodén L (1983) Assay of N-acetyl heparosan deacetylase with a capsular polysaccharide from Escherichia coli K5 as substrate. Anal Biochem 135: 134–140
Chromczynski P, Sacchi N (1987) Single step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Annal Biochem 162: 156–159
Kohno K, Sullivan M, Yamada Y (1985) Structure of the promoter of the rat type II procollagen gene. J Biol Chem 260: 4441–4447
Noonan DM, Horigan EA, Ledbetter SR et al. (1988) Identification of cDNA clones encoding different domains of the basement menbrane heparan sulfate proteoglycan. J Biol Chem 263: 16379–16387
Danielson PE, Forss-Petter S, Brow MA et al. (1988) p1 B15: a cDNA clone of the rat mRNA encoding cyclophillin. DNA 7: 261–267
Ihm C-G, Lee GSL, Nast CC et al. (1992) Early increased renal procollagen Ó1(IV) mRNA levels in streptozotocin induced diabetes. Kidney Int 41: 768–777
Ledbetter S, Copeland EJ, Noonan D, Vogeli, Hassell J (1990) Altered steady-state mRNA levels of basement membrane proteins in diabetic mouse kidneys and thromboxane synthease inhibition. Diabetes 39: 196–203
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Kofoed-Enevoldsen, A., Noonan, D. & Deckert, T. Diabetes mellitus induced inhibition of glucosaminyl N-deacetylase: effect of short-term blood glucose control in diabetic rats. Diabetologia 36, 310–315 (1993). https://doi.org/10.1007/BF00400233
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DOI: https://doi.org/10.1007/BF00400233