Division of Endocrinology, Department of Medicine, University of Florida-Jacksonville College of Medicine, Jacksonville, FL 32209, USA.
Metabolism. 2013 Feb;62(2):265-74. doi: 10.1016/j.metabol.2012.07.005. Epub 2012 Aug 16.
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.
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.
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.
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.
糖尿病血脂异常是发生大血管并发症的一个重要危险因素。最近的临床试验表明，接受胰高血糖素样肽-1（GLP-1）治疗的糖尿病患者的血脂水平正常化，包括血浆高密度脂蛋白胆固醇（HDLc）水平升高。
为了确定 GLP-1（7-36 酰胺）和 GLP-1 样胰岛素促分泌肽 exendin-4 是否调节载脂蛋白 A-I（apo A-I）的表达，apo A-I 是高密度脂蛋白（HDL）的主要抗动脉粥样硬化成分，用越来越多的每种肽处理 HepG2 肝细胞和 Caco-2 肠细胞，这两种细胞代表表达大多数 apo A-I 的组织，并在条件培养基中测量 apo A-I 基因表达。
apo A-I 在 GLP-1 和 exendin-4 处理的 HepG2 细胞中均有分泌增加，但在 Caco-2 细胞中没有，并且 apo A-I mRNA 水平和 apo A-I 启动子活性也发生了类似的变化。GLP-1 和 exendin-4 诱导 apo A-I 启动子活性需要一个 SP1 反应元件。GLP-1 和 exendin-4 还诱导了肝 ATP 结合盒蛋白 A1（ABCA1）的表达，但不诱导清道夫受体 B 型 1 受体的表达。
这些结果表明，GLP-1 和 exendin-4 介导的 HDLc 变化可能是由于肝 apo A-I 和 ABCA1 表达的变化所致。
