| 1. |
- Ahrén, Bo
(author)
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GLP-1 and extra-islet effects.
- 2004
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In: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 36:11-12, s. 842-845
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Research review (peer-reviewed)
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| 2. |
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| 3. |
- Ahrén, Bo, et al.
(author)
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Improved meal-related insulin processing contributes to the enhancement of B-Cell function by the DPP-4 inhibitor vildagliptin in patients with type 2 diabetes
- 2007
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In: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 39:11, s. 826-829
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Journal article (peer-reviewed)abstract
- The aim of this study was to evaluate the contribution of insulin processing to the improved meal-related B-cell function previously shown with the DPP-4 inhibitor vildagliptin. Fifty-five patients with type 2 diabetes (56.5 +/- 1.5 years; BMI=29.6 +/- 0.5kg/m(2); FPG = 9.9 +/- 0.2 mmol/l; HbA1c=7.7 +/- 0.1 %) were studied: 29 pateients were treated with vildagliptin and 26 patients with placebo, both added to an ongoing metformin regimen (1.5-3.0g/day). A standardized breakfast was given at baseline and after 52 weeks of treatment, and proinsulin related to insulin secretion was measured with C-peptide in the fasting and postprandial (over 4h post-meal) states to evaluate B-cell function. The between-treatment difference (vildaglip-tin-placebo) in mean change from baseline in fasting proinsulin to C-peptide ratio (fastP/C) was -0.007 +/- 0.009 (p=0.052). Following the standard breakfast, 52 weeks of treatment with vildagliptin significantly decreased the dynamic proinsulin to C-peptide ratio (dynP/C) relative to placebo by 0.010 +/- 0.008 (p = 0.037). Importantly, when the P/C was expressed in relation to the glucose stimulus (i.e., the fasting glucose and glucose AUC(0-240min), respectively), the P/C relative to glucose was significantly reduced with vildagliptin vs. placebo, both in the fasting state (p = 0.023) and postprandially (p = 0.004). In conclusion, a more efficient B-cell insulin processing provides further evidence that vildagliptin treatment ameliorates abnormal B-cell function in patients with type 2 diabetes.
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| 4. |
- Ahrén, Bo, et al.
(author)
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Incretin hormones and insulin secretion.
- 2004
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In: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 36:11-12, s. 733-734
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Journal article (peer-reviewed)
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| 5. |
- Arnqvist, Hans
(author)
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The role of IGF-system in vascular insulin resistance
- 2008
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In: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 40:9, s. 588-592
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Research review (peer-reviewed)abstract
- Insulin and IGF-I are closely related peptides, which interact by several mechanisms. In high supraphysiological concentrations (=10-8M), they cross-react with each other's receptors with 100- to 1000-fold lower affinity than with their cognate receptors. This can cause confusion, since in many in vitro studies, insulin has been used in high unphysiological concentrations, which activate IGF-I receptors. Due to the differences in affinity, insulin and IGF-I probably do not activate each other's receptors in vivo. IGF-I receptors are several-fold more abundant than insulin receptors in human micro- and macrovascular endothelial cells and in human vascular smooth muscle cells. Both insulin and IGF-I receptor protein can be demonstrated and they are activated by their cognate ligand at physiological concentrations of 10-9-10-10M. In vascular smooth muscle cells, IGF-I but not insulin stimulates metabolism and growth. IGF-I stimulates DNA-synthesis and growth in microvascular endothelial cells, but neither insulin nor IGF-I have any effect on macrovascular endothelial cells. Both insulin and IGF-I have been shown to stimulate nitric oxide production in endothelial cells, but only the effect of IGF-I was obtained at a physiological concentration. In both endothelial and vascular smooth muscle cells, insulin and IGF-I receptors occur as insulin/ICF-I hybrid receptors with high affinity to IGF-I and low for insulin. Due to the low number of insulin receptors and the presence of hybrid receptors the insulin receptor signal is probably too attenuated to elicit biological effects, explaining the insulin resistance of vascular cells in vitro. In vivo both insulin and IGF-I have been reported to increase muscle blood flow in physiological concentrations. Whether this is due to direct effects on endothelial cells or indirectly induced is not clear. The effect of insulin is attenuated by insulin resistance. In conclusion, the in vitro data suggest that endothelial cells and vascular smooth muscle cells are sensitive to IGF-I, but insensitive to insulin, and this is due to a preponderance of IGF-I receptors and the presence of insulin/IGF-l hybrid receptors. © Georg Thieme Verlag KG Stuttgart · New York.
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| 7. |
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| 8. |
- Efendic, S, et al.
(author)
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Overview of incretin hormones
- 2004
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In: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. - : Georg Thieme Verlag KG. - 0018-5043. ; 36:11-12, s. 742-746
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Journal article (peer-reviewed)
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| 9. |
- Elfving, Maria, et al.
(author)
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Epitope Analysis of GAD65 Binding in both Cord Blood and at the Time of Clinical Diagnosis of Childhood Type 1 Diabetes.
- 2007
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In: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 1439-4286 .- 0018-5043. ; 39:11, s. 790-796
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Journal article (peer-reviewed)abstract
- The GAD65 epitope immunoglobulin binding pattern in cord blood of children (n=37), who later developed type 1 diabetes at 3.2-14.9 years of age, was analyzed. First, the binding at diagnosis was compared with that in the cord blood serum. The next comparison was between the cord blood serum and the mothers' serum taken at delivery. Basal GAD65 binding levels were determined in Protein A Sepharose-based radio-binding assays with S-35-labeled human and rat GAD65, rat GAD67 and GAD65/67 fusion proteins representing N-terminal (N), middle (M) and C-terminal (C) epitopes. In the first comparison, 28/37 children had GAD65 binding above 2.44 relative units (RU) (upper three quartiles), representing a marked increase from birth in the binding to human GAD65 (p < 0.0001), rat GAD65 (p < 0.0001), N- (p = 0.04), M- (p < 0.0001), C- (p=0.001), and M + C-epitopes (p < 0.0001), but not to rat GAD67. At birth, 9/37 had GAD65 binding above 1.56 RU (upper quartile) demonstrating that their binding of human S-35-GAD65 was higher in cord blood than in the mother (p=0.008). Higher cord blood binding was also observed for the N- (p=0.02) terminal epitope but not for rat GAD65, rat GAD67, and the remaining epitopes. These data suggest that differences in the epitope GAD65 binding between mother and child at birth are limited. In contrast, the epitope pattern at diagnosis differed from that at birth, supporting the view that disease-associated epitopes develop between birth and diagnosis.
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| 10. |
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