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

• DOI: 10.1210/jc.2017-01551
• Publication Date: 2017-10-25T18:17:25Z
• Authors: Sangeeta R Kashyap; Abdullah Osme; Serguei Ilchenko; Makan Golizeh; Kwangwon Lee; Shuhui Wang; James Bena; Stephen F Previs; Jonathan D Smith; Takhar Kasumov
• Keywords: Glycated hemoglobin; Amadori rearrangement

Hyperglycemia plays a key role in the pathogenesis of cardiovascular complications diabetes. Type 2 diabetes mellitus (T2DM) is associated with high-density lipoprotein (HDL) dysfunction and increased degradation apolipoprotein I (ApoAI). The mechanism(s) these changes largely unknown. To study hyperglycemia-induced glycation on ApoAI kinetics stability patients diet-controlled T2DM. 2H2O-metabolic labeling approach was used to turnover T2DM [n = 9 (5 F); 59.3 ± 8.5 years] matched healthy controls 8 (4 50.7 11.6 years]. effect Amadori vivo antioxidant cholesterol efflux properties HDL were assessed using proteomics vitro assays. Patients had impaired HDL. Glycated hemoglobin negatively correlated half-life function Proteomics analysis identified several nonenzymatic early (Amadori) glycations at lysine sites. glycated native peptides revealed that resulted threefold shorter half-life. 2H2O method allowed detection impairments metabolism related