title: Treatment With Metformin Improves Erectile Dysfunction in a Murine Model of Obesity Associated With Insulin Resistance.
abstract: OBJECTIVE
  To evaluate the effects of treatment with metformin on a murine model of obesity-associated erectile dysfunction.
  
  
  METHODS
  C57BL/6 male mice were fed for 10 weeks with standard chow or high-fat diet. Lean and obese mice were treated with the insulin sensitizer metformin (300 mg/kg/day, 2 weeks). Intracavernosal pressure (ICP) and in vitro corpus cavernosum (CC) relaxations to both acetylcholine and electrical field stimulation, as well as phenylephrine-induced contractions, were obtained. Levels of cyclic guanosine monophosphate in CC were detected by enzyme immunoassay.
  
  
  RESULTS
  High-fat-fed mice exhibited higher body weight and insulin resistance. Cavernous nerve stimulation caused frequency-dependent ICP increases, which were significantly lower in obese compared with lean mice (P <.05). Two-week therapy with metformin reversed the decreased ICP in obese group. The maximal response to acetylcholine in CC was 35% lower (P <.05) in the obese compared to the lean group, which were restored by metformin treatment. Likewise, the impaired electrical field stimulation-induced CC relaxations in obese mice were also partly restored by metformin. Contractile responses to phenylephrine were significantly greater (P <.05) in obese compared to lean mice, which were fully restored by metformin. Basal and stimulated cyclic guanosine monophosphate productions in the erectile tissues were significantly lower (P <.05) in the obese group, an effect fully restored by metformin.
  
  
  CONCLUSIONS
  Treatment with metformin restored the erectile function in obese mice, through improvement of in vitro endothelial and nitrergic cavernosal relaxations. Therefore, use of metformin may be a good pharmacologic approach to treat insulin resistance-associated erectile dysfunction.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil. Electronic address: fabiohsilva87@gmail.com.
authors.forename: Fábio H
authors.initials: FH
authors.lastname: Silva
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Alexandre
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Fabiano B
authors.initials: FB
authors.lastname: Calmasini
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Calixto
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Edson
authors.initials: E
authors.lastname: Antunes
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000209:etiology*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications* / Q000378:metabolism*
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin