Chaudhuri Ajay, Ghanim Husam, Makdissi Antoine, Green Kelly, Abuaysheh Sanaa, Batra Manav, D Kuhadiya Nitesh, Dandona Paresh
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo, Buffalo, New York.
Diabetes Obes Metab. 2017 May;19(5):729-733. doi: 10.1111/dom.12835. Epub 2017 Feb 22.
In view of the known vasodilatory effects of glucagon-like peptide-1 and exenatide, we investigated the effects of exenatide on vasoactive factors. We analysed blood samples and mononuclear cells (MNCs) from a previous study, collected after a single dose and 12 weeks of exenatide or placebo treatment in a series of 24 patients with type 2 diabetes mellitus. After exenatide treatment, plasma concentrations of atrial natriuretic peptide, cyclic guanyl monophosphate (cGMP) and cyclic adenyl monophosphate increased significantly at 12 weeks. Plasma cGMP and adenylate cyclase expression in MNCs increased significantly after a single dose. Angiotensinogen concentration fell significantly 2 hours after a single dose and at 12 weeks, while renin and angiotensin II levels fell significantly only after a single dose and not after 12 weeks of treatment. Exenatide also suppressed the plasma concentration of transforming growth factor-β and the expression of P311 in MNCs at 12 weeks. Thus, exenatide induces an increase in a series of vasodilators, while suppressing the renin-angiotensin system. These changes may contribute to the overall vasodilatory effect of exenatide.
鉴于胰高血糖素样肽-1和艾塞那肽已知的血管舒张作用，我们研究了艾塞那肽对血管活性因子的影响。我们分析了先前一项研究中的血样和单核细胞（MNC），这些样本是在24例2型糖尿病患者接受单剂量和12周的艾塞那肽或安慰剂治疗后采集的。艾塞那肽治疗后，12周时血浆心房利钠肽、环磷酸鸟苷（cGMP）和环磷酸腺苷浓度显著升高。单剂量给药后，MNC中的血浆cGMP和腺苷酸环化酶表达显著增加。单剂量给药2小时后及12周时，血管紧张素原浓度显著下降，而肾素和血管紧张素II水平仅在单剂量给药后显著下降，治疗12周后未下降。12周时，艾塞那肽还抑制了血浆转化生长因子-β浓度和MNC中P311的表达。因此，艾塞那肽可诱导一系列血管舒张剂增加，同时抑制肾素-血管紧张素系统。这些变化可能有助于艾塞那肽的整体血管舒张作用。
