| Title |
Anti-angiogenic effects of the DPP-4 inhibitor linagliptin via inhibition of VEGFR signalling in the mouse model of oxygen-induced retinopathy
|
|---|---|
| Published in |
Diabetologia, August 2018
|
| DOI | 10.1007/s00125-018-4701-4 |
| Pubmed ID | |
| Authors |
Matthias Kolibabka, Nadine Dietrich, Thomas Klein, Hans-Peter Hammes |
| Abstract |
Linagliptin has protective effects on the retinal neurovascular unit but, in proliferative retinopathy, dipeptidyl peptidase 4 (DPP-4) inhibition could be detrimental. The aim of this study was to assess the effect of linagliptin on ischaemia-induced neovascularisation of the retina. C57BL/6J and glucagon-like peptide 1 (GLP-1) receptor (Glp1r)-/- mice were subjected to a model of oxygen-induced retinopathy (OIR). Both strains were subcutaneously treated with linagliptin from postnatal days 12 to 16. Non-injected OIR and non-exposed mice served as controls. Capillary proliferations and systemic levels of active GLP-1 were quantified. The effects of linagliptin on vascular endothelial growth factor (VEGF)-induced downstream signalling were assessed in human umbilical vein endothelial cells (HUVECs) using western blot for retinal phosphorylated extracellular signal-regulated kinase (ERK)1/2 and retinal gene expression analyses. Linagliptin treatment led to an increase in active GLP-1 and a decreased number of neovascular nuclei in OIR mice vs controls (-30%, p < 0.05). As the reduction in neovascularisation was similar in both C57BL/6J and Glp1r-/- mice, the anti-angiogenic effects of linagliptin were independent of GLP-1R status. The expression of Vegf (also known as Vegfa) and Hif1a was increased in C57BL/6J OIR mice upon linagliptin treatment (three- vs 1.5-fold, p < 0.05, p < 0.01, respectively). In HUVECs, linagliptin inhibited VEGF-induced increases in mitogen-activated protein kinase (MAPK)/ERK (-67%, p < 0.001) and MAPK/c-Jun N-terminal kinase (JNK) (-13%, p < 0.05) pathway activities. In the retinas of C57BL/6J mice, p-ERK1/2 levels were significantly reduced upon linagliptin treatment (-47%, p < 0.05). Systemic treatment with linagliptin demonstrated GLP-1R-independent anti-angiogenic effects mediated by an inhibition of VEGF receptor downstream signalling. The specific effects of linagliptin on diabetic retinopathy are of potential benefit for individuals with diabetes, independent of metabolic effects. |
X Demographics
The data shown below were collected from the profiles of 6 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Canada | 1 | 17% |
| Unknown | 5 | 83% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 5 | 83% |
| Scientists | 1 | 17% |
Mendeley readers
The data shown below were compiled from readership statistics for 26 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 26 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 4 | 15% |
| Researcher | 3 | 12% |
| Other | 2 | 8% |
| Student > Doctoral Student | 2 | 8% |
| Student > Ph. D. Student | 1 | 4% |
| Other | 2 | 8% |
| Unknown | 12 | 46% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 4 | 15% |
| Pharmacology, Toxicology and Pharmaceutical Science | 3 | 12% |
| Neuroscience | 3 | 12% |
| Biochemistry, Genetics and Molecular Biology | 2 | 8% |
| Immunology and Microbiology | 1 | 4% |
| Other | 1 | 4% |
| Unknown | 12 | 46% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 August 2018.
All research outputs
#12,988,420
of 23,099,576 outputs
Outputs from Diabetologia
#4,165
of 5,096 outputs
Outputs of similar age
#156,448
of 331,118 outputs
Outputs of similar age from Diabetologia
#54
of 63 outputs
Altmetric has tracked 23,099,576 research outputs across all sources so far. This one is in the 43rd percentile – i.e., 43% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one is in the 14th percentile – i.e., 14% of its contemporaries scored the same or lower than it.