Diabetes Results in Structural Alteration of Chondroitin Sulfate in the Urine

Purpose. The assessment of the clinical significance of chondroitin sulfate in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between chondroitin sulfate (CS) structure and disease. Methods. Healthy control (n=15), type 2 diabetic pa...

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Main Authors: Tingting Zhao, Xiaoguang Lu, Neal M Davies, Yuewen Gong, Jingzhen Guo, Haojun Zhang, Zhiguo Li, Jing Hong, Guixiang Fu, Ping Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2013-07-01
Series:Journal of Pharmacy & Pharmaceutical Sciences
Online Access:https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/19447
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author Tingting Zhao
Xiaoguang Lu
Neal M Davies
Yuewen Gong
Jingzhen Guo
Haojun Zhang
Zhiguo Li
Jing Hong
Guixiang Fu
Ping Li
author_facet Tingting Zhao
Xiaoguang Lu
Neal M Davies
Yuewen Gong
Jingzhen Guo
Haojun Zhang
Zhiguo Li
Jing Hong
Guixiang Fu
Ping Li
author_sort Tingting Zhao
collection DOAJ
description Purpose. The assessment of the clinical significance of chondroitin sulfate in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between chondroitin sulfate (CS) structure and disease. Methods. Healthy control (n=15), type 2 diabetic patients with normalbuminuria (n=12), and patients with microalbuminuria (n=13) were enrolled in the study. Total sulfated glycosaminoglycans (GAGs) concentration in the first morning urine was evaluated by 1,9-dimethylmethylene blue method and the composition was determined by agarose gel electrophoresis. Urinary chondroitin sulfate was quantified by a combination of treatment with specific lyase digestions and separation of products by SAX-HPLC. Results: GAGs concentration significantly increased in diabetic patients with microalbuminuria compared to diabetic patients with normalbuminuria. Qualitative analysis of urinary GAGs revealed the presence of chondroitin sulfate, heparan sulfate, and low-sulphated chondroitin sulphate-protein complex (LSC-PG). There was a decrease in CS and an increase in LSC-PG in the urine of patients with diabetes compared to healthy controls. Moreover, in diabetic patients, chondroitin sulfate contains more 6-sulfated disaccharide and less 4-sulfated disaccharide. There was a statistically significant difference in ratio of 6-sulfated disaccharide to 4-sulfated disaccharide among the three groups. Conclusions: GAGs were significantly increased in diabetic patients with microalbuminuria. The levels of urinary GAGs, ratio of LSC-PG/CS, as well as ratio of 6-sulfated to 4-sulfated disaccharides could be useful markers for diagnosis of patients with diabetic nephropathy.   This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.
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spelling doaj.art-51f368639cad43d9a35a4b6e6378aaae2023-09-02T02:37:23ZengFrontiers Media S.A.Journal of Pharmacy & Pharmaceutical Sciences1482-18262013-07-0116310.18433/J3GS3CDiabetes Results in Structural Alteration of Chondroitin Sulfate in the UrineTingting Zhao0Xiaoguang Lu1Neal M Davies2Yuewen Gong3Jingzhen Guo4Haojun Zhang5Zhiguo Li6Jing Hong7Guixiang Fu8Ping Li9Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.Faculty of Pharmacy, University of Manitoba, Winnipeg, Canada.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.Purpose. The assessment of the clinical significance of chondroitin sulfate in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) for the detection of the relationship between chondroitin sulfate (CS) structure and disease. Methods. Healthy control (n=15), type 2 diabetic patients with normalbuminuria (n=12), and patients with microalbuminuria (n=13) were enrolled in the study. Total sulfated glycosaminoglycans (GAGs) concentration in the first morning urine was evaluated by 1,9-dimethylmethylene blue method and the composition was determined by agarose gel electrophoresis. Urinary chondroitin sulfate was quantified by a combination of treatment with specific lyase digestions and separation of products by SAX-HPLC. Results: GAGs concentration significantly increased in diabetic patients with microalbuminuria compared to diabetic patients with normalbuminuria. Qualitative analysis of urinary GAGs revealed the presence of chondroitin sulfate, heparan sulfate, and low-sulphated chondroitin sulphate-protein complex (LSC-PG). There was a decrease in CS and an increase in LSC-PG in the urine of patients with diabetes compared to healthy controls. Moreover, in diabetic patients, chondroitin sulfate contains more 6-sulfated disaccharide and less 4-sulfated disaccharide. There was a statistically significant difference in ratio of 6-sulfated disaccharide to 4-sulfated disaccharide among the three groups. Conclusions: GAGs were significantly increased in diabetic patients with microalbuminuria. The levels of urinary GAGs, ratio of LSC-PG/CS, as well as ratio of 6-sulfated to 4-sulfated disaccharides could be useful markers for diagnosis of patients with diabetic nephropathy.   This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/19447
spellingShingle Tingting Zhao
Xiaoguang Lu
Neal M Davies
Yuewen Gong
Jingzhen Guo
Haojun Zhang
Zhiguo Li
Jing Hong
Guixiang Fu
Ping Li
Diabetes Results in Structural Alteration of Chondroitin Sulfate in the Urine
Journal of Pharmacy & Pharmaceutical Sciences
title Diabetes Results in Structural Alteration of Chondroitin Sulfate in the Urine
title_full Diabetes Results in Structural Alteration of Chondroitin Sulfate in the Urine
title_fullStr Diabetes Results in Structural Alteration of Chondroitin Sulfate in the Urine
title_full_unstemmed Diabetes Results in Structural Alteration of Chondroitin Sulfate in the Urine
title_short Diabetes Results in Structural Alteration of Chondroitin Sulfate in the Urine
title_sort diabetes results in structural alteration of chondroitin sulfate in the urine
url https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/19447
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