Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 35 P697 | DOI: 10.1530/endoabs.35.P697

ECE2014 Poster Presentations Male reproduction (25 abstracts)

Metformin in vitro and in vivo increases adenosine signalling in rabbit corpora cavernosa

Linda Vignozzi 1 , Sandra Filippi 2 , Paolo Comeglio 1 , Ilaria Cellai 1 , Giulia Rastrelli 1 , Annamaria Morelli 3 , Edoardo Mannucci 4 & Mario Maggi 1

1Department Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy; 2Department Neurofarba, University of Florence, Florence, Italy; 3Department Experimental and Clinical Medicine, University of Florence, Florence, Italy; 4Department Critical Care, Diabetes Section, Geriatric Unit, Careggi Hospital, Florence, Italy.

Introduction: In subjects with erectile dysfunction (ED) responding poorly to sildenafil, metformin was reported to improve erections.

Aims: To investigate metformin’s mechanism of action on erectile function, particularly focusing on adenosine (ADO), and NO signalling in an animal model of high fat diet (HFD)-induced metabolic syndrome (MetS).

Methods: In vitro contractility studies of penile strips. Penile expression of genes related to ADO- or NO-signalling was also evaluated.

Main outcome measure: In vitro contractility studies were used to investigate the effect of in vivo and ex vivo metformin administration on ADO- or acetylcholine (Ach)-induced relaxation of penile strips from HFD, as compared to animals fed a regular diet (RD).

Results: Expression of ADO receptor type 3 (A3R), ADO deaminase (ADA), AMP deaminase type 1 (AMPD1), and 2 (AMPD2) was decreased in HFD, as compared to RD. Accordingly, in HFD the ADO relaxant effect was potentiated as compared to RD (P<0.02). In vivo metformin treatment in both RD and HFD significantly increased the ADO relaxing effect (P<0.0001, and P<0.01 respectively, vs relative untreated groups), although to a different extent. In fact, the IC50/IC50 ratio in RD increased four folds vs HFD (RD IC50 ratio=13.75±2.96; HFD IC50 ratio=2.85±0.52). In CC from HFD, in vivo metformin i) normalized A3R, ADA, and AMPD1, ii) further decreased AMPD2, iii) increased dimethylarginine dimethylamino-hydrolase (DDAH1), and iv) partially restored impaired Ach-induced relaxation. Ex vivo metformin time- and dose-dependently increased the relaxant effect of ADO in RD. The potentiating effect of metformin on ADO-induced relaxation was significantly reduced by pre-incubation with NOS inhibitor L-NAME. Interestingly, in vivo testosterone supplementation in HFD rabbits: i) increased penile expression of AMPD2, and ii) restored ADO-induced relation, up to RD level.

Conclusion: Metformin in vitro and in vivo increases ADO signalling in CC, most probably interfering with ADO breakdown and NO formation.

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