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, 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 (1.0 mg o.d.), and ramipril Plus tadalafil. RESULTS - Ramipril decreased systolic and diastolic blood pressure, ACE activity, and angiotensin It 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 mu . minol(-1) . l(-1), respectively, for tadalafil treatment vs. placebo; P = 0.01) but not in men, There was no effect of an), treatment on Fibrinolysis. CONCLUSIONS - Phosphodiesterase 5 inhibition may represent a novel strategy for improving beta-cell function in metabolic syndrome.