title: The selective phosphodiesterase-5 inhibitor tadalafil induces microvascular and metabolic effects in type 2 diabetic postmenopausal females.
abstract: OBJECTIVE
  The objective of the study was to explore the acute in vivo effects of the selective phosphodiesterase-5 inhibitor tadalafil on local microcirculation and regional metabolism in skeletal muscle and adipose tissue (AT).
  
  
  METHODS
  We studied eight postmenopausal female patients with type 2 diabetes (T2D) and eight nondiabetic controls (Ctrl) in the postabsorptive state and 180 min after the administration of tadalafil 10 mg. Intramuscular and sc microdialysis were combined with measurements of forearm (FBF) and AT blood flow as well as with arterial and deep venous blood sampling. Muscle capillary recruitment, as ascertained by the permeability surface area product for glucose (PS(glu)), forearm glucose uptake (FGU), interstitial lactate, and glycerol concentrations, was measured.
  
  
  RESULTS
  When compared with Ctrl, T2D patients exhibited lower (P = 0.01) PS(glu) but similar FGU and FBF. After tadalafil, PS(glu) (P = 0.01) and muscle interstitial-arterial (I-A) lactate concentration gradient (P < 0.01) increased significantly in both groups, whereas FBF, FGU, and I-A glycerol remained unchanged. In AT, tadalafil did not significantly affect local blood flow, whereas the sc interstitial (I) lactate and I-A lactate concentrations increased (P < 0.01), and the I-A glycerol decreased in both groups. Finally, in multivariate analysis the PS(glu) was a strong and independent predictor of muscle glucose disposal (β: 0.737 and 0.963, P < 0.05, in Ctrl and T2D, respectively).
  
  
  CONCLUSIONS
  Tadalafil emerges as an acutely acting modulator of microvascular recruitment and glucose metabolism in skeletal muscle and adipose tissue. We suggest that selective phosphodiesterase-5 blockade may provide a path forward to new therapeutics in the setting of insulin resistance.
authors.affiliation: Department of Internal Medicine, Diabetes, Endocrinology, and Obesity, Assisi Hospital, V. Muller 1, I-06081 Assisi (Perugia), Italy. gmurdolo@tiscali.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Murdolo
authors.forename: Mikaela
authors.initials: M
authors.lastname: Sjöstrand
authors.forename: Lena
authors.initials: L
authors.lastname: Strindberg
authors.forename: Peter
authors.initials: P
authors.lastname: Lönnroth
authors.forename: Per-Anders
authors.initials: PA
authors.lastname: Jansson
mesh_terms: D000273:Adipose Tissue / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects / Q000502:physiology; D002243:Carbolines / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000139:chemically induced / Q000378:metabolism; D005260:Female; D006801:Humans; D017551:Microdialysis; D055806:Microvessels / Q000187:drug effects*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000150:complications; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology; D013379:Substrate Specificity; D000068581:Tadalafil
chemical_list: D002243:Carbolines; D058986:Phosphodiesterase 5 Inhibitors; D000068581:Tadalafil