Dataset Information

Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes.

ABSTRACT:

Aims/hypothesis

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/interpretation

This study suggests that tadalafil evokes positive metabolic effects in insulin-resistant women with type 2 diabetes.

SUBMITTER: Jansson PA

PROVIDER: S-EPMC2931646 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes.

Jansson P-A PA Murdolo G G Sjögren L L Nyström B B Sjöstrand M M Strindberg L L Lönnroth P P

Diabetologia 20100610 10

<h4>Aims/hypothesis</h4>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.<h4>Methods</h4>We enrolled seven postmenopausal women with type 2 diabetes and ten age-m ...[more]

PMID: 20535445

Similar Datasets

Project description:BACKGROUND: Retinoid X receptor (RXR) ? is a nuclear receptor-type transcription factor expressed mostly in skeletal muscle, and regulated by nutritional conditions. Previously, we established transgenic mice overexpressing RXR? in skeletal muscle (RXR? mice), which showed lower blood glucose than the control mice. Here we investigated their glucose metabolism. METHODOLOGY/PRINCIPAL FINDINGS: RXR? mice were subjected to glucose and insulin tolerance tests, and glucose transporter expression levels, hyperinsulinemic-euglycemic clamp and glucose uptake were analyzed. Microarray and bioinformatics analyses were done. The glucose tolerance test revealed higher glucose disposal in RXR? mice than in control mice, but insulin tolerance test revealed no difference in the insulin-induced hypoglycemic response. In the hyperinsulinemic-euglycemic clamp study, the basal glucose disposal rate was higher in RXR? mice than in control mice, indicating an insulin-independent increase in glucose uptake. There was no difference in the rate of glucose infusion needed to maintain euglycemia (glucose infusion rate) between the RXR? and control mice, which is consistent with the result of the insulin tolerance test. Skeletal muscle from RXR? mice showed increased Glut1 expression, with increased glucose uptake, in an insulin-independent manner. Moreover, we performed in vivo luciferase reporter analysis using Glut1 promoter (Glut1-Luc). Combination of RXR? and PPAR? resulted in an increase in Glut1-Luc activity in skeletal muscle in vivo. Microarray data showed that RXR? overexpression increased a diverse set of genes, including glucose metabolism genes, whose promoter contained putative PPAR-binding motifs. CONCLUSIONS/SIGNIFICANCE: Systemic glucose metabolism was increased in transgenic mice overexpressing RXR?. The enhanced glucose tolerance in RXR? mice may be mediated at least in part by increased Glut1 in skeletal muscle. These results show the importance of skeletal muscle gene regulation in systemic glucose metabolism. Increasing RXR? expression may be a novel therapeutic strategy against type 2 diabetes.

Dataset Information

Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes.

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets