Type 2 Diabetes Is Associated with Reduced ATP-Binding Cassette Transporter A1 Gene Expression, Protein and Function
Open Access
- 27 July 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (7), e22142
- https://doi.org/10.1371/journal.pone.0022142
Abstract
Increasing plasma glucose levels are associated with increasing risk of vascular disease. We tested the hypothesis that there is a glycaemia-mediated impairment of reverse cholesterol transport (RCT). We studied the influence of plasma glucose on expression and function of a key mediator in RCT, the ATP binding cassette transporter-A1 (ABCA1) and expression of its regulators, liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor–γ (PPARγ). Leukocyte ABCA1, LXRα and PPARγ expression was measured by polymerase chain reaction in 63 men with varying degrees of glucose homeostasis. ABCA1 protein concentrations were measured in leukocytes. In a sub-group of 25 men, ABCA1 function was quantified as apolipoprotein-A1-mediated cholesterol efflux from 2–3 week cultured skin fibroblasts. Leukocyte ABCA1 expression correlated negatively with circulating HbA1c and glucose (rho = −0.41, pLXRα and PPARγ expression. ABCA1 expression and protein concentrations in leukocytes, as well as function in cultured skin fibroblasts, are reduced in T2DM. ABCA1 protein concentration and function are associated with HDL-C levels. These findings indicate a glycaemia- related, persistent disruption of a key component of RCT.Keywords
This publication has 52 references indexed in Scilit:
- Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and AtherosclerosisNew England Journal of Medicine, 2011
- Diabetes reduces the cholesterol exporter ABCA1 in mouse macrophages and kidneysJournal of Lipid Research, 2010
- Anti-diabetic drugs inhibit obesity-linked phosphorylation of PPARγ by Cdk5Nature, 2010
- An intracellular role for ABCG1-mediated cholesterol transport in the regulated secretory pathway of mouse pancreatic β cellsJCI Insight, 2010
- Adipocyte Modulation of High-Density Lipoprotein CholesterolCirculation, 2010
- Carriers of Loss-of-Function Mutations in ABCA1 Display Pancreatic β-Cell DysfunctionDiabetes Care, 2010
- Renal Dysfunction Potentiates Foam Cell Formation by Repressing ABCA1Arteriosclerosis, Thrombosis, and Vascular Biology, 2009
- High glucose, unsaturated and saturated fatty acids differentially regulate expression of ATP-binding cassette transporters ABCA1 and ABCG1 in human macrophagesExperimental & Molecular Medicine, 2009
- 10-Year Follow-up of Intensive Glucose Control in Type 2 DiabetesNew England Journal of Medicine, 2008
- Reduced Expression of ATP-Binding Cassette Transporter G1 Increases Cholesterol Accumulation in Macrophages of Patients With Type 2 Diabetes MellitusCirculation, 2008