Comprehensive glycomic analysis reveals that human serum albumin glycation specifically affects the pharmacokinetics and efficacy of different anticoagulant drugs in diabetes
Authors
Qiu, Hongyan
Jin, Lan
Chen, Jian
Shi, Min
Shi, Feng
Wang, Mansen
Li, Daoyuan
Xu, Xiaohui
Su, Xinhuan
Yin, Xianlun
ORCID
https://orcid.org/0000-0003-2219-5833
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Other Contributors
Issue Date
2020-04-01
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Degree
Terms of Use
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Full Citation
Comprehensive glycomic analysis reveals that human serum albumin glycation specifically affects the pharmacokinetics and efficacy of different anticoagulant drugs in diabetes, H. Qiu, L. Jin, J. Chen, M. Shi, F. Shi, M. Wang, D. Li, X. Xu, X. Su, X. Yin, W. Li, X. Zhou, R. J. Linhardt, Z. Wang, L.Chi, Q. Zhang, Diabetes, 69, 760-770, 2020.
Abstract
Long-term hyperglycemia in patients with diabetes leads to human serum albumin (HSA) glycation, which may impair HSA function as a transport protein and affect the therapeutic efficacy of anticoagulants in patients with diabetes. In this study, a novel mass spectrometry approach was developed to reveal the differences in the profiles of HSA glycation sites between patients with diabetes and healthy subjects. K199 was the glycation site most significantly changed in patients with diabetes, contributing to different interactions of glycated HSA and normal HSA with two types of anticoagulant drugs, heparin and warfarin. An in vitro experiment showed that the binding affinity to warfarin became stronger when HSA was glycated, while HSA binding to heparin was not significantly influenced by glycation. A pharmacokinetic study showed a decreased level of free warfarin in the plasma of diabetic rats. A preliminary retrospective clinical study also revealed that there was a statistically significant difference in the anticoagulant efficacy between patients with diabetes and patients without diabetes who had been treated with warfarin. Our work suggests that larger studies are needed to provide additional specific guidance for patients with diabetes when they are administered anticoagulant drugs or drugs for treating other chronic diseases.
Description
Diabetes, 69, 760-770
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Department
The Linhardt Research Labs.
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
The Shirley Ann Jackson, Ph.D. Center for Biotechnology and Interdisciplinary Studies (CBIS)
Publisher
Relationships
The Linhardt Research Labs Online Collection
Rensselaer Polytechnic Institute, Troy, NY
Diabetes
https://harc.rpi.edu/
Rensselaer Polytechnic Institute, Troy, NY
Diabetes
https://harc.rpi.edu/