Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes.
OBJECTIVE
Recent evidence suggests that reduced synthesis of nitric oxide in endothelial cells, i.e. endothelial dysfunction, contributes to the impaired action of insulin in the vasculature of patients with type 2 diabetes. We investigated whether selective inhibition of phosphodiesterase-5 by tadalafil has beneficial effects on peripheral microcirculation and glucose uptake in these patients.


METHODS
We enrolled seven postmenopausal women with type 2 diabetes and ten age-matched healthy women as controls in a placebo-controlled study to evaluate the acute metabolic effects of tadalafil. We performed microdialysis and blood flow measurements in muscle, and sampled arterial and deep venous blood before and after a single dose of tadalafil 20 mg or placebo. Circulating glucose and insulin levels, muscle capillary recruitment as reflected by permeability surface area for glucose (PS(glu)) and forearm glucose uptake were measured.


RESULTS
In women with type 2 diabetes, but not in the control group, tadalafil induced increases in the incremental AUC for PS(glu) (tadalafil vs placebo 41 +/- 11 vs 4 +/- 2 ml [100 g](-1) min(-1), p < 0.05) and forearm glucose uptake (46 +/- 9 vs 8 +/- 4 micromol [100 g](-1) min(-1), p < 0.05). The variable that best predicted forearm glucose uptake was PS(glu), which explained 70% of its variance. However, fasting glucose and insulin concentrations were similar following treatment with placebo or tadalafil in the two groups.


CONCLUSIONS
This study suggests that tadalafil evokes positive metabolic effects in insulin-resistant women with type 2 diabetes.
The Lundberg Laboratory for Diabetes Research, Center of Excellence for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Blå Stråket 5, S-413 45 Göteborg, Sweden. per-anders.jansson@medic.gu.se
P-A
PA
Jansson
G
G
Murdolo
L
L
Sjögren
B
B
Nyström
M
M
Sjöstrand
L
L
Strindberg
P
P
Lönnroth
D000368:Aged; D019540:Area Under Curve; D002196:Capillaries / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002243:Carbolines / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005542:Forearm / Q000098:blood supply* / Q000503:physiopathology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D017551:Microdialysis; D008875:Middle Aged; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D000068581:Tadalafil
D002243:Carbolines; D010726:Phosphodiesterase Inhibitors; D000068581:Tadalafil; D005947:Glucose