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. 2018 Mar;59(3):602-613.
doi: 10.1007/s12020-017-1378-2. Epub 2017 Aug 7.

The phosphodiesterase 5 inhibitor tadalafil regulates lipidic homeostasis in human skeletal muscle cell metabolism

F Marampon  1 , C Antinozzi  1 , C Corinaldesi  1   2 , G B Vannelli  3 , E Sarchielli  3 , S Migliaccio  1 , L Di Luigi  1 , A Lenzi  4 , C Crescioli  5
Affiliations

The phosphodiesterase 5 inhibitor tadalafil regulates lipidic homeostasis in human skeletal muscle cell metabolism

F Marampon et al. Endocrine. 2018 Mar.

Abstract

Purpose: Tadalafil seems to ameliorate insulin resistance and glucose homeostasis in humans. We have previously reported that tadalafil targets human skeletal muscle cells with an insulin (I)-like effect. We aim to evaluate in human fetal skeletal muscle cells after tadalafil or I: (i) expression profile of I-regulated genes dedicated to cellular energy control, glycolitic activity or microtubule formation/vesicle transport, as GLUT4, PPARγ, HK2, IRS-1, KIF1C, and KIFAP3; (ii) GLUT4, Flotillin-1, and Caveolin-1 localization, all proteins involved in energy-dependent cell trafficking; (iii) activation of I-targeted paths, as IRS-1, PKB/AKT, mTOR, P70/S6K. Free fatty acids intracellular level was measured. Sildenafil or a cGMP synthetic analog were used for comparison; PDE5 and PDE11 gene expression was evaluated in human fetal skeletal muscle cells.

Methods: RTq-PCR, PCR, western blot, free fatty acid assay commercial kit, and lipid stain non-fluorescent assay were used.

Results: Tadalafil upregulated I-targeted investigated genes with the same temporal pattern as I (GLUT4, PPARγ, and IRS-1 at 3 h; HK2, KIF1C, KIFAP3 at 12 h), re-localized GLUT4 in cell sites positively immune-decorated for Caveolin-1 and Flotillin-1, suggesting the involvement of lipid rafts, induced specific residue phosphorylation of IRS-1/AKT/mTOR complex in association with free fatty acid de novo synthesis. Sildenafil or GMP analog did not affect GLUT4 trafficking or free fatty acid levels.

Conclusion: In human fetal skeletal muscle cells tadalafil likely favors energy storage by modulating lipid homeostasis via IRS-1-mediated mechanisms, involving activation of I-targeted genes and intracellular cascade related to metabolic control. Those data provide some biomolecular evidences explaining, in part, tadalafil-induced favorable control of human metabolism shown by clinical studies.

Keywords: Insulin; Metabolism; PDE5i; Skeletal muscle; Tadalafil.

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References

    1. BJU Int. 2005 Aug;96(3):257-80 - PubMed
    1. Diabetes. 2007 Apr;56(4):1025-33 - PubMed
    1. Diabetes. 1999 Apr;48(4):699-705 - PubMed
    1. Clin Sports Med. 2008 Jan;27(1):131-51, ix - PubMed
    1. Exp Neurol. 2008 Sep;213(1):241-4 - PubMed

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