Induction of apolipoprotein A-I gene expression by glucagon-like peptide-1 and exendin-4 in hepatocytes but not intestinal cells
Induction of apolipoprotein A-I gene expression by glucagon-like peptide-1 and exendin-4 in hepatocytes but not intestinal cells
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DOI：
10.1016/j.metabol.2012.07.005
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发表时间：
2013-02-01
影响因子：
9.8
通讯作者：
Haas, Michael J.
中科院分区：
文献类型：
--
作者：
Chehade, Joe M.;Alcalde, Rosalyn;Haas, Michael J.
Objective.糖尿病血脂异常是发生大血管并发症的重要危险因素。最近的临床试验表明，用胰高血糖素样肽-1（GLP-1）治疗的糖尿病患者血脂水平正常，包括血浆高密度脂蛋白胆固醇（HDLc）水平升高。为了确定GLP-1是否（7-36酰胺）和GLP-1样促胰岛素肽毒蜥外泌肽-4调节载脂蛋白A-I（apo A-I）的表达，载脂蛋白A-I是高密度脂蛋白（HDL）、HepG 2肝细胞和Caco-2肠细胞的主要抗动脉粥样硬化组分，代表表达大部分apo A-I的组织，用递增量的每种肽处理，并在条件培养基中测量apo A-I基因表达。在GLP-1和exendin-4处理的HepG 2细胞中，Apo A-I分泌增加，但Caco-2细胞没有增加，这伴随着apo A-I mRNA水平和apo A-I启动子活性的相似变化。GLP-1和exendin-4对apo A-I启动子活性的诱导需要SP1反应元件。GLP-1和exendin-4可诱导肝脏ATP结合盒蛋白A1（ABCA 1）表达，但不诱导清道夫受体B 1型受体表达。这些结果表明，GLP-1和exendin-4介导的HDL c变化可能是由于载脂蛋白A-I和ABCA 1的肝脏表达变化所致。(c)2013 Elsevier Inc. All rights reserved.
Objective. Diabetic dyslipidemia is an important risk factor for the development of macrovascular complications. Recent clinical trials suggest that diabetics treated with glucagon-like peptide-1 (GLP-1) have normalized lipid levels, including an increase in plasma high-density lipoprotein cholesterol (HDLc) levels.Methods. To determine if GLP-1 (7-36 amide) and the GLP-1-like insulinotropic peptide exendin-4 regulate expression of apolipoprotein A-I (apo A-I), the primary anti-atherogenic component of high-density lipoprotein (HDL), HepG2 hepatocytes and Caco-2 intestinal cells, representative of tissues that express the majority of apo A-I, were treated with increasing amounts of each peptide and apo A-I gene expression was measured in the conditioned medium.Results. Apo A-I secretion increased in both GLP-1 and exendin-4-treated HepG2, but not Caco-2 cells, and this was accompanied by similar changes in apo A-I mRNA levels and apo A-I promoter activity. Induction of apo A-I promoter activity by GLP-1 and exendin-4 required an SP1-responsive element. Hepatic ATP binding cassette protein A1 (ABCA1) expression, but not scavenger receptor class B type1 receptor expression was also induced by GLP-1 and exendin-4.Conclusions. These results suggest that GLP-1- and exendin-4-mediated changes in HDLc are likely due to changes in hepatic expression of apo A-I and ABCA1. (c) 2013 Elsevier Inc. All rights reserved.