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Text
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URL Address
<a href="http://doi.org/10.1210/jc.2017-01551" target="_blank" rel="noreferrer noopener">http://doi.org/10.1210/jc.2017-01551</a>
Pages
388–396
Issue
2
Volume
103
Dublin Core
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Title
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Glycation Reduces the Stability of ApoAI and Increases HDL Dysfunction in Diet-Controlled Type 2 Diabetes.
Publisher
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The Journal of clinical endocrinology and metabolism
Date
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2018
2018-02
Subject
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Adult; Aged; Animal Studies; Animals; Apolipoprotein A-I/blood/*metabolism; Apolipoproteins – Blood; Apolipoproteins – Metabolism; Biochemical Phenomena; Case Control Studies; Case-Control Studies; Cells; Comparative Studies; Cultured; Diabetes Mellitus; Diet; Dyslipidemias/complications/diet therapy/*metabolism; Evaluation Research; Female; Funding Source; Glycosylation; HDL – Metabolism; HDL/*metabolism; Human; Humans; Hyperglycemia – Complications; Hyperglycemia – Diet Therapy; Hyperglycemia – Metabolism; Hyperglycemia/complications/diet therapy/*metabolism; Hyperlipidemia – Complications; Hyperlipidemia – Diet Therapy; Hyperlipidemia – Metabolism; Lipoproteins; Male; Mice; Middle Age; Middle Aged; Multicenter Studies; Protein Stability; Type 2 – Complications; Type 2 – Diet Therapy; Type 2 – Metabolism; Type 2/complications/*diet therapy/metabolism; Validation Studies
Creator
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Kashyap Sangeeta R; Osme Abdullah; Ilchenko Serguei; Golizeh Makan; Lee Kwangwon; Wang Shuhui; Bena James; Previs Stephen F; Smith Jonathan D; Kasumov Takhar
Description
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Context: Hyperglycemia plays a key role in the pathogenesis of cardiovascular complications of diabetes. Type 2 diabetes mellitus (T2DM) is associated with high-density lipoprotein (HDL) dysfunction and increased degradation of apolipoprotein I (ApoAI). The mechanism(s) of these changes is largely unknown. Objective: To study the role of hyperglycemia-induced glycation on ApoAI kinetics and stability in patients with diet-controlled T2DM. Design: 2H2O-metabolic labeling approach was used to study ApoAI turnover in patients with diet-controlled T2DM [n = 9 (5 F); 59.3 +/- 8.5 years] and matched healthy controls [n = 8 (4 F); 50.7 +/- 11.6 years]. The effect of Amadori glycation on in vivo ApoAI stability and the antioxidant and cholesterol efflux properties of HDL were assessed using a proteomics approach and in vitro assays. Results: Patients with T2DM had increased turnover of ApoAI and impaired cholesterol efflux and antioxidant properties of HDL. Glycated hemoglobin was negatively correlated with the half-life of ApoAI and cholesterol efflux function of HDL. Proteomics analysis identified several nonenzymatic early (Amadori) glycations of ApoAI at lysine sites. The kinetics analysis of glycated and native ApoAI peptides in patients with T2DM revealed that glycation resulted in a threefold shorter ApoAI half-life. Conclusions: The 2H2O method allowed the detection of early in vivo impairments in HDL metabolism and function that were related to hyperglycemia-induced glycation of ApoAI in T2DM.
Identifier
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<a href="http://doi.org/10.1210/jc.2017-01551" target="_blank" rel="noreferrer noopener">10.1210/jc.2017-01551</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
2018
Adult
Aged
Animal Studies
Animals
Apolipoprotein A-I/blood/*metabolism
Apolipoproteins – Blood
Apolipoproteins – Metabolism
Bena James
Biochemical Phenomena
Case Control Studies
Case-Control Studies
Cells
Comparative Studies
Cultured
Department of Pharmaceutical Sciences
Diabetes Mellitus
Diet
Dyslipidemias/complications/diet therapy/*metabolism
Evaluation Research
Female
Funding Source
Glycosylation
Golizeh Makan
HDL – Metabolism
HDL/*metabolism
Human
Humans
Hyperglycemia – Complications
Hyperglycemia – Diet Therapy
Hyperglycemia – Metabolism
Hyperglycemia/complications/diet therapy/*metabolism
Hyperlipidemia – Complications
Hyperlipidemia – Diet Therapy
Hyperlipidemia – Metabolism
Ilchenko Serguei
Kashyap Sangeeta R
Kasumov Takhar
Lee Kwangwon
Lipoproteins
Male
Mice
Middle Age
Middle Aged
Multicenter Studies
NEOMED College of Pharmacy
Osme Abdullah
Previs Stephen F
Protein Stability
Smith Jonathan D
The Journal of clinical endocrinology and metabolism
Type 2 – Complications
Type 2 – Diet Therapy
Type 2 – Metabolism
Type 2/complications/*diet therapy/metabolism
Validation Studies
Wang Shuhui