Hill Kevin D, Eckhauser Aaron W, Marney Annis, Brown Nancy J
Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Diabetes Care. 2009 May;32(5):857-9. doi: 10.2337/dc08-1862. Epub 2009 Feb 5.
This study tested the hypothesis that phosphodiesterase 5 inhibition alone or in combination with ACE inhibition improves glucose homeostasis and fibrinolysis in individuals with metabolic syndrome.
Insulin sensitivity, beta-cell function, and fibrinolytic parameters were measured in 18 adults with metabolic syndrome on 4 separate days after a randomized, crossover, double-blind, 3-week treatment with placebo, ramipril (10 mg/day), tadalafil (10 mg o.d.), and ramipril plus tadalafil.
Ramipril decreased systolic and diastolic blood pressure, ACE activity, and angiotensin II and increased plasma renin activity. Ramipril did not affect insulin sensitivity or beta-cell function. In contrast, tadalafil improved beta-cell function (P = 0.01). This effect was observed in women (331.9 +/- 209.3 vs. 154.4 +/- 48.0 32 micro x mmol(-1) x l(-1), respectively, for tadalafil treatment vs. placebo; P = 0.01) but not in men. There was no effect of any treatment on fibrinolysis. CONCLUSIONS Phosphodiesterase 5 inhibition may represent a novel strategy for improving beta-cell function in metabolic syndrome.
本研究检验了以下假设，即单独使用磷酸二酯酶5抑制剂或与血管紧张素转换酶（ACE）抑制剂联合使用，可改善代谢综合征患者的葡萄糖稳态和纤维蛋白溶解功能。
对18名患有代谢综合征的成年人进行随机、交叉、双盲、为期3周的安慰剂、雷米普利（10毫克/天）、他达拉非（10毫克/天）以及雷米普利加他达拉非治疗，在4个不同日期测量胰岛素敏感性、β细胞功能和纤维蛋白溶解参数。
雷米普利降低收缩压和舒张压、ACE活性及血管紧张素II水平，并提高血浆肾素活性。雷米普利不影响胰岛素敏感性或β细胞功能。相比之下，他达拉非改善了β细胞功能（P = 0.01）。这种效应在女性中观察到（他达拉非治疗组与安慰剂组分别为331.9±209.3和154.4±48.0 32微摩尔×毫摩尔-1×升-1；P = 0.01），但在男性中未观察到。任何治疗对纤维蛋白溶解均无影响。结论：磷酸二酯酶5抑制可能是改善代谢综合征患者β细胞功能的一种新策略。
