Glycation Reduces the Stability of ApoAI and Increases HDL Dysfunction in Diet-Controlled Type 2 Diabetes.

Title

Glycation Reduces the Stability of ApoAI and Increases HDL Dysfunction in Diet-Controlled Type 2 Diabetes.

Creator

Kashyap Sangeeta R; Osme Abdullah; Ilchenko Serguei; Golizeh Makan; Lee Kwangwon; Wang Shuhui; Bena James; Previs Stephen F; Smith Jonathan D; Kasumov Takhar

Publisher

The Journal of clinical endocrinology and metabolism

Date

2018
2018-02

Description

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.

Subject

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

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

388–396

Issue

2

Volume

103

Citation

Kashyap Sangeeta R; Osme Abdullah; Ilchenko Serguei; Golizeh Makan; Lee Kwangwon; Wang Shuhui; Bena James; Previs Stephen F; Smith Jonathan D; Kasumov Takhar, “Glycation Reduces the Stability of ApoAI and Increases HDL Dysfunction in Diet-Controlled Type 2 Diabetes.,” NEOMED Bibliography Database, accessed September 26, 2021, https://neomed.omeka.net/items/show/4902.

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