Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: Insulin sensitivity, β-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. RESULTS: Ramipril decreased systolic and diastolic blood pressure, ACE activity, and angiotensin II and increased plasma renin activity. Ramipril did not affect insulin sensitivity or β-cell function. In contrast, tadalafil improved β-cell function (P = 0.01). This effect was observed in women (331.9 ± 209.3 vs. 154.4 ± 48.0 32 μ · mmol(−1) · 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 β-cell function in metabolic syndrome.