Influence of glucose on production and N-sulfation of heparan sulfate in cultured adipocyte cells

Citation
N. Parthasarathy et al., Influence of glucose on production and N-sulfation of heparan sulfate in cultured adipocyte cells, MOL C BIOCH, 213(1-2), 2000, pp. 1-9
Citations number
69
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR AND CELLULAR BIOCHEMISTRY
ISSN journal
03008177 → ACNP
Volume
213
Issue
1-2
Year of publication
2000
Pages
1 - 9
Database
ISI
SICI code
0300-8177(200010)213:1-2<1:IOGOPA>2.0.ZU;2-X
Abstract
Altered lipoprotein lipase regulation associated with diabetes leading to t he development of hypertriglyceridemia might be attributed to possible chan ges in content and the fine structure of heparan sulfate and its associated lipoprotein lipase. Adipocyte cell surface is the primary site of synthesi s of lipoprotein lipase and the enzyme is bound to cell surface heparan sul fate proteoglycans via heparan sulfate side chains. In this study, the effe ct of diabetes on the production of adipocyte heparan sulfate and its sulfa tion (especially N-sulfation) were examined. Mouse 3T3-L1 adipocytes were e xposed to high glucose (25 mM) and low glucose (5.55 mM) in the medium and cell-associated heparan sulfate was isolated and characterized. A significa nt decrease in total content of heparan sulfate was observed in adipocytes cultured under high glucose as compared to low glucose conditions. The degr ee of N-sulfation was assessed through oligosaccharide mapping of heparan s ulfate after chemical cleavages involving low pH (1.5) nitrous acid and hyd razinolysis/high pH (4.0) nitrous acid treatments; N-sulfation was found to be comparable between the adipocyte heparan sulfates produced under these glucose conditions. The activity and message levels for N-deacetylase/N-sul fotransferase, the enzyme responsible for N-sulfation in the biosynthesis o f heparan sulfate, did not vary in adipocytes whether they were exposed to low or high glucose. While most cells or tissues in diabetic situations pro duce heparan sulfate with low-charge density concomitant with a decrease in N-sulfation, adipocyte cell system is an exception in this regard. Heparan sulfate from adipocytes cultured in low glucose conditions binds to lipopr otein lipase by the same order of magnitude as that derived from high gluco se conditions. It is apparent that adipocytes cultured under high glucose c onditions produce diminished levels of heparan sulfate (without significant changes in N-sulfation). In conclusion, it is possible that the reduction in heparan sulfate in diabetes could contribute to the decreased levels of heparan sulfate associated lipoprotein lipase, leading to diabetic hypertri glyceridemia.