Phosphodiesterase 5 Inhibition Improves Beta Cell Function in the Metabolic Syndrome

Abstract

Objective: This study tested the hypothesis that phosphodiesterase 5 inhibition alone or in combination with angiotensin-converting enzyme 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 eighteen adults with metabolic syndrome on four separate days after randomized, crossover, double-blind, 3-week treatment with placebo, ramipril (10mg/d), tadalafil (10mg/od), and ramipril+tadalafil.

Results: Ramipril decreased systolic and diastolic blood pressure, angiotensin-converting enzyme 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±209.3mu/mM during tadalafil versus 154.4±48.0mu/mM during 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.