Kimura Tomohiko, Obata Atsushi, Shimoda Masashi, Okauchi Seizo, Hirukawa Hidenori, Kohara Kenji, Kinoshita Tomoe, Nogami Yuka, Nakanishi Shuhei, Mune Tomoatsu, Kaku Kohei, Kaneto Hideaki
1 Division of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan.
2 Department of General Internal Medicine 1, Kawasaki Hospital, Kawasaki Medical School, Okayama, Japan.
Diab Vasc Dis Res. 2017 Nov;14(6):540-548. doi: 10.1177/1479164117725898. Epub 2017 Aug 23.
Incretin signalling is known to prevent the development of arteriosclerosis by relaxation response in endothelial cells via the glucagon-like peptide 1 receptor. It remains unclear, however, whether vascular glucagon-like peptide 1 receptor expression is altered under some conditions. The aim of this study is to examine whether vascular glucagon-like peptide 1 receptor expression is altered by diabetic state as reported in pancreatic β-cells.
We used 18-week-old male diabetic db/db mice and control db/m mice. Excised thoracic artery was specifically collected, and vascular endothelial cells were cultured. We compared the glucagon-like peptide 1 receptor expression levels between the db/db and db/m mice.
Metabolic parameters were significantly worse in db/db mice. The glucagon-like peptide 1 receptor and transcription factor 7-like 2 expression levels in endothelial and smooth muscle cells were significantly lower in db/db mice. Furthermore, siRNA to transcription factor 7-like 2 decreased the transcription factor 7-like 2 levels and such reduction of the transcription factor 7-like 2 resulted in the downregulation of the glucagon-like peptide 1 receptor expressions in cultured vascular endothelial cells.
The glucagon-like peptide 1 receptor expression level was significantly lower under diabetic condition which was accompanied by the reduction of the transcription factor 7-like 2 expression level. Furthermore, the transcription factor 7-like 2 is a possible regulator of the glucagon-like peptide 1 receptor expression in artery as reported in β-cells.
已知肠促胰岛素信号通过胰高血糖素样肽1受体在内皮细胞中的舒张反应来预防动脉硬化的发展。然而，尚不清楚在某些情况下血管胰高血糖素样肽1受体的表达是否会发生改变。本研究的目的是检验血管胰高血糖素样肽1受体的表达是否如胰腺β细胞中报道的那样因糖尿病状态而改变。
我们使用了18周龄的雄性糖尿病db/db小鼠和对照db/m小鼠。专门收集切除的胸主动脉，并培养血管内皮细胞。我们比较了db/db小鼠和db/m小鼠之间胰高血糖素样肽1受体的表达水平。
db/db小鼠的代谢参数明显更差。db/db小鼠内皮细胞和平滑肌细胞中胰高血糖素样肽1受体和转录因子7样2的表达水平明显更低。此外，针对转录因子7样2的小干扰RNA降低了转录因子7样2的水平，而转录因子7样2的这种降低导致培养的血管内皮细胞中胰高血糖素样肽1受体表达下调。
在糖尿病状态下，胰高血糖素样肽1受体的表达水平明显更低，这伴随着转录因子7样2表达水平的降低。此外，转录因子7样2可能如β细胞中报道的那样是动脉中胰高血糖素样肽1受体表达的调节因子。
