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- Sjögren, Lovisa, et al.
(författare)
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Postprandial effects of the phosphodiesterase-5 inhibitor tadalafil in people with well-controlled Type 2 diabetes mellitus: a randomized controlled trial.
- 2016
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Ingår i: Diabetic medicine : a journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; 33:9
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes mellitus is a serious global health problem that is hard to treat in the long term, prompting great efforts to find new drug targets. Little attention has been paid, however, to the metabolic significance of the microcirculation in insulin-sensitive tissues, despite the fact that microvascular insulin resistance and endothelial dysfunction are closely associated and have been shown to precede Type 2 diabetes [1]. Endothelial nitric oxide plays a major role in mediating the beneficial effects of insulin on capillary recruitment and muscle glucose uptake [2] and in suppression of inflammatory pathways, including those activated by a high-fat diet [3]. This article is protected by copyright. All rights reserved.
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| 2. |
- Jansson, Per-Anders, 1961, et al.
(författare)
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Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes
- 2010
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Ingår i: DIABETOLOGIA. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:10, s. 2205-2208
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Tidskriftsartikel (refereegranskat)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 (PSglu) 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 PSglu (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 µmol [100 g]−1 min−1, p < 0.05). The variable that best predicted forearm glucose uptake was PSglu, 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.
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| 3. |
- Sjöstrand, M, et al.
(författare)
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Repeated measurements of 11β-HSD-1 activity in subcutaneous adipose tissue from lean, abdominally obese, and type 2 diabetes subjects--no change following a mixed meal.
- 2010
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Ingår i: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et métabolisme. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 42:11, s. 798-802
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to measure 11β-HSD-1 activity in subcutaneous adipose tissue by an ex vivo method in three subgroups; lean, obese, and type 2 diabetes subjects, both in the fasting state and after a mixed meal and to determine the variability and reproducibility of this method. Eighteen subjects were investigated; 6 lean, 6 abdominally obese, and 6 type 2 diabetes subjects (BMI 22 ± 1, 30 ± 3 and 31 ± 3 kg/m², respectively). Needle biopsies were taken repeatedly and an index of 11β-HSD-1 activity was measured as percent conversion of (3)H-cortisone to (3)H-cortisol/100 mg tissue. For two separate biopsies taken in the fasting state on the same day, the within subjects CV was 16% and the between CV was 36% for 11β-HSD-1 activity for all subjects. For two biopsies taken in the fasting state at two different days, the total within subjects CV was 38% and the between subjects CV was 46%. Lean subjects had lower 11β-HSD-1 activity (4.8 ± 1.5% conversion of ³H-cortisone to ³H-cortisol/100 mg tissue) than both obese (14.4 ± 1.6% conversion, p<0.01) and type 2 diabetes subjects (11.7 ± 1.9% conversion, p<0.05) in the fasting state. There was no effect of a meal on 11β-HSD-1 activity in any of the three groups. The conclusions from this study are: 1) the variation coefficient for the ex vivo adipose tissue 11β-HSD-1 activity method was ∼25% for repeat measures within subjects; 2) food intake had no major impact on enzyme activity; and 3) 11β-HSD-1 activity in subcutaneous adipose tissue was significantly increased in obese subjects with or without T2DM compared to lean subjects without diabetes.
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