二肽基肽酶-4（DPP-4）保护的胰高血糖素样肽-1（7-36）对肥胖成年人冠状动脉微血管功能的影响
The effect of DPP-4-protected GLP-1 (7-36) on coronary microvascular function in obese adults.
作者信息
Nilsson Malin, Bové Kira Bang, Suhrs Elena, Hermann Thomas, Madsbad Sten, Holst Jens Juul, Prescott Eva, Zander Mette
机构信息
Department of Endocrinology, Bispebjerg University Hospital, Copenhagen, Denmark.
Department of Cardiology, Bispebjerg University Hospital, Copenhagen, Denmark.
出版信息
Int J Cardiol Heart Vasc. 2019 Jan 29;22:139-144. doi: 10.1016/j.ijcha.2019.01.004. eCollection 2019 Mar.
OBJECTIVE
Glucagon-like-peptide-1 (GLP-1) receptor analogues have been shown to reduce cardiovascular events in patients with type 2 diabetes. However, the mechanism behind is still unknown. The aim of the study was to investigate the effect of intact GLP-1 (7-36) on coronary microcirculation in overweight adults.
DESIGN AND METHODS
A double-blinded randomized cross-over study was performed, with 12 overweight participants. Effects of intact GLP-1 (7-36) infusion were compared with a saline infusion on separate days. A DPP-4 inhibitor was administered to block degradation of intact GLP-1 (7-36) to the GLP-1 metabolite (9-36). Coronary microcirculation was assessed by Doppler coronary flow velocity reserve (CFVR) before and after 2 h of infusion. Peripheral endothelial function was assessed by flow mediated dilation (FMD) before and after one hour of infusion.
RESULTS
CFVR was 3.77 ± 1.25 during GLP-1 infusion and 3.85 ± 1.32 during saline infusion, endothelial function was 16.3 ± 15.5 % during GLP-1 infusion and 7.85 ± 7.76 % during saline infusion. When adjusting for baseline values no significant differences in CFVR (ΔCFVR 0.38 ± 0.92 vs. ΔCFVR 0.71 ± 1.03, = 0.43) and no difference in peripheral endothelial function (ΔFMD 7.34 ± 11.5 % vs. ΔFMD -1.25 ± 9.23%, = 0.14) was found.
CONCLUSIONS
We found no effect of intact GLP-1 (7-36), protected from DPP4 mediated degradation on coronary microcirculation in overweight adults.
目的
胰高血糖素样肽-1（GLP-1）受体类似物已被证明可降低2型糖尿病患者的心血管事件。然而，其背后的机制仍不清楚。本研究的目的是调查完整的GLP-1（7-36）对超重成年人冠状动脉微循环的影响。
设计与方法
进行了一项双盲随机交叉研究，有12名超重参与者。在不同日期将完整的GLP-1（7-36）输注的效果与生理盐水输注进行比较。给予二肽基肽酶-4（DPP-4）抑制剂以阻断完整的GLP-1（7-36）降解为GLP-1代谢物（9-36）。在输注2小时前后通过多普勒冠状动脉血流速度储备（CFVR）评估冠状动脉微循环。在输注1小时前后通过血流介导的血管舒张（FMD）评估外周内皮功能。
结果
GLP-1输注期间CFVR为3.77±1.25，生理盐水输注期间为3.85±1.32；GLP-1输注期间内皮功能为16.3±15.5%，生理盐水输注期间为7.85±7.76%。在调整基线值后，未发现CFVR有显著差异（ΔCFVR 0.38±0.92 vs. ΔCFVR 0.71±1.03，P = 0.43），外周内皮功能也无差异（ΔFMD 7.34±11.5% vs. ΔFMD -1.25±9.23%，P = 0.14）。
结论
我们发现免受DPP4介导降解的完整GLP-1（7-36）对超重成年人的冠状动脉微循环没有影响。
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