Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome

doi:10.2337/dc08-1862

Phosphodiesterase 5 Inhibition Improves β-Cell Function in Metabolic Syndrome

¹Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee;
²Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee;
³Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.

Corresponding author: Nancy J. Brown, nancy.j.brown{at}vanderbilt.edu

Abstract

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.

Footnotes

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Clinical trial reg. no. NCT00750308, clinicaltrials.gov.
- Received October 17, 2008.
- Accepted January 26, 2009.
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