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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Research Article

ABCG1 is Expressed in an LXR-Independent Manner in Patients with Type 2 Diabetes Mellitus

Author(s): Hui-Juan Wang, Ji-Hong Wang, Xin-Na Xu, Xing-Shan Zhao and Wei Liu*

Volume 23, Issue 8, 2023

Published on: 09 September, 2022

Page: [815 - 824] Pages: 10

DOI: 10.2174/1566524023666220822150820

Price: $65

Abstract

Background: Patients with type 2 diabetes mellitus have a high cardiovascular risk due, in part, to abnormalities of high-density lipoprotein mediated cholesterol efflux. The ATP-binding cassette A1 and G1 play a pivotal role in the regulation of cholesterol efflux. However, the regulation of these transporters in type 2 diabetes mellitus remains obscure.

Objectives: This study aimed to investigate the expression of ATP-binding cassette A1 and G1 and their regulation by Liver X receptors in monocyte-derived macrophages in type 2 diabetes mellitus, and to determine whether the alteration of these transporters might affect cholesterol efflux from macrophages.

Methods: Blood was collected from type 2 diabetic patients and healthy controls. Peripheral monocytes were differentiated into macrophages. Quantitative real-time PCR, western blots, and cholesterol efflux assays were performed. The Liver X receptor and Liver X receptor element complex in the ATP-binding cassette G1 gene promoter were detected by electrophoretic mobility supershift assay.

Results: Macrophage ATP-binding cassette G1 expression and high density lipoproteininduced cholesterol efflux were significantly reduced in type 2 diabetic patients. However, the mRNA expression of ATP-binding cassette G1 in type 2 diabetic patients was not inhibited by Liver X receptor siRNA and the Liver X receptor- Liver X receptor element complexes remain unchanged similarly.

Conclusion: The study suggested that the expression of ATP-binding cassette G1 and high density lipoprotein-induced cholesterol efflux in macrophages were reduced in type 2 diabetes mellitus. Impairment of cholesterol efflux and ATP-binding cassette G1 gene expression in type 2 diabetes mellitus might be regulated by a Liver X receptorindependent pathway.

Keywords: Cholesterol efflux, high-density lipoprotein, ATP binding cassette transporter G1, diabetes mellitus, liver X receptors, macrophages.

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