Leukocyte ATP-binding cassette transporter G1 gene expression is reduced in type 2 diabetes mellitus

Abstract

Leukocyte ATP-Binding Cassette Transporter G1 Gene Expression is Reduced in Type 2 Diabetes Mellitus Reverse cholesterol transport Reverse cholesterol transport is a pathway which transports cholesterol from extrahepatic cells and tissues to the liver for excretion. Cellular cholesterol efflux represents the first critical step of reverse cholesterol transport and is regulated by cholesterol transporters including ATP-binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor class B type I (SR-BI). We have investigated whether the expression of these transporters is affected by type 2 diabetes and the association with glycaemic indexes and oxidzied LDL (oxLDL).<br />The mRNA of ABCA1, ABCG1 and SR-BI in peripheral monocytes was measured in 30 diabetic patients and 30 matched controls. Cellular cholesterol efflux from monocytes to 5% diluted pooled standard serum or autologous serum was determined ex vivo. Cellular cholesterol was labeled with tracer [3H]cholesterol during the incubation with acetylated LDL, and 5% diluted pooled standard serum or autologous serum was then used to induce cholesterol efflux from the labeled cells for 4 hours. Plasma oxLDL and advanced glycation end products (AGEs) were assayed by ELISA.<br />The expression of ABCG1 was decreased in diabetic patients (p<0.05), whereas the levels of ABCA1 and SR-BI were comparable between the two groups. Fasting glucose, HbA1c, AGEs and oxLDL were all significantly increased in diabetic patients. There was an inverse correlation between serum AGEs and ABCG1 (r=-0.44, p<0.05) which remained significant after adjusting for potential confounding factors. No associations between fasting glucose, HbA1c, plasma lipids or oxLDL and the expression of ABCG1, ABCA1 or SR-BI expression were found. Cholesterol efflux from monocytes to standard serum or autologous serum was significantly impaired in diabetic patients (p<0.05) and the reduction in efflux to autologous serum correlated with the expression of ABCG1 (r=0.60, p<0.05).<br />In conclusion, the expression of ABCG1 in monocytes is reduced in type 2 diabetes and is partly related to serum AGEs concentration. The reduction in ABCG1 is associated with impairment in cholesterol efflux and may contribute to accelerated foam cell formation in diabetic patients.