Lim Dong-Mee, Park Keun-Young, Hwang Won-Min, Kim Ju-Young, Kim Byung-Joon
Division of Endocrinology, Department of Internal Medicine, Konyang University School of Medicine, Daejeon 35365, Republic of Korea.
Division of Nephrology, Department of Internal Medicine, Konyang University School of Medicine, Daejeon 35365, Republic of Korea.
Exp Ther Med. 2017 May;13(5):2558-2564. doi: 10.3892/etm.2017.4279. Epub 2017 Mar 29.
Receptors for glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are present in vascular endothelial cells. Previous studies investigating euglycemic status have demonstrated that GIP is directly involved in the physiology of blood vessels by controlling the blood flow rate of portal veins and that GLP-1 has a protective effect on blood vessels by acting on endothelial cells. However, to the best of our knowledge, the effects of GIP and GLP-1 on endothelial cells in patients with hyperglycemia remain unknown. Therefore, the present study investigated whether the effect of the incretin hormones GLP-1 and GIP differed with regards to the reversal of endothelial cell dysfunction caused by hyperglycemia. The production of nitric oxide (NO) was measured using the Griess reagent system kit and the expression of cyclic adenosine monophosphate (cAMP) in the cell was measured at a wavelength of 405 nm with the ELISA reader using the cyclic AMP EIA kit. Exposure of human umbilical vein endothelial cells (HUVEC) to a high glucose concentration decreased NO and endothelial nitric oxide synthase (eNOS) levels but increased inducible NOS (iNOS) levels. However, when HUVECs were pretreated with GLP-1, a reduction of iNOS expression was observed and the expression of eNOS and NO were increased, as opposed to pretreatment with GIP. The results differed according to the response of cAMP, the second messenger of incretin hormones: The GIP pretreatment group did not exhibit an increase in cAMP levels while the GLP-1 pretreatment group did. The results of the present study provide evidence that GLP-1, but not GIP, has a protective effect on endothelial function associated with cardiovascular disease, as it is associated with increased eNOS expression and the levels of NO. This effect may be due to an increase in the cAMP concentration during hyperglycemic events.
葡萄糖依赖性促胰岛素多肽（GIP）和胰高血糖素样肽1（GLP-1）的受体存在于血管内皮细胞中。先前研究正常血糖状态的研究表明，GIP通过控制门静脉血流速度直接参与血管生理过程，并且GLP-1通过作用于内皮细胞对血管具有保护作用。然而，据我们所知，GIP和GLP-1对高血糖患者内皮细胞的影响仍然未知。因此，本研究调查了肠促胰岛素激素GLP-1和GIP在逆转高血糖引起的内皮细胞功能障碍方面的作用是否存在差异。使用格里斯试剂系统试剂盒测量一氧化氮（NO）的产生，并使用环磷酸腺苷酶联免疫吸附测定试剂盒，在405nm波长下用酶标仪测量细胞中环磷酸腺苷（cAMP）的表达。将人脐静脉内皮细胞（HUVEC）暴露于高葡萄糖浓度会降低NO和内皮型一氧化氮合酶（eNOS）水平，但会增加诱导型一氧化氮合酶（iNOS）水平。然而，与用GIP预处理相反，当用GLP-1预处理HUVEC时，观察到iNOS表达降低，eNOS和NO的表达增加。结果根据肠促胰岛素激素的第二信使cAMP的反应而有所不同：GIP预处理组的cAMP水平没有增加，而GLP-1预处理组的cAMP水平增加。本研究结果提供了证据，表明GLP-1而非GIP对与心血管疾病相关的内皮功能具有保护作用，因为它与eNOS表达增加和NO水平升高有关。这种作用可能是由于高血糖事件期间cAMP浓度增加所致。
