Hyperglycemia causes micro- and macrovascular complications in diabetic patients. Elevated glucose (gluc) concentrations lead to increased formation of the highly reactive dicarbonyl methylglyoxal (MG); yet, the early consequences of MG for development of vascular complications in vivo is poorly understood. In this study zebrafish was used as a model organism to analyze early vascular effects and mechanisms of MG in vivo. High tissue glucose increased MG concentrations in tg(fli:EGFP) zebrafish embryos and rapidly induced several additional malformed and uncoordinated blood vessel structures that originated out of existing intersomitic blood vessels. However, larger blood vessels including the dorsal aorta and common cardinal vein were not affected. Expression silencing of MG degrading enzyme glyoxalase 1 (glo1) elevated MG concentrations and induced a similar vascular hyperbranching phenotype in zebrafish. MG enhanced phosphorylation of VEGF receptor 2 and its downstream target Akt/PKB. Pharmacological inhibitors for VEGF receptor 2 and Akt/PKB as well as MG scavenger aminoguanidine and glo1 activation prevented MG induced hyperbranching of intersomitic blood vessels. Taken together, MG acts on smaller blood vessels in zebrafish via the VEGF receptor signalling cascade, thereby describing a new mechanism that can explain vascular complications under hyperglycemia and elevated MG concentrations.
Pharmacology, Toxicology and Pharmaceutical Science
4
6%
Veterinary Science and Veterinary Medicine
2
3%
Other
3
5%
Unknown
15
24%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. 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 18 January 2019.
All research outputs
#9,032,743
of 30,202,275 outputs
Outputs from Diabetes
#4,472
of 10,844 outputs
Outputs of similar age
#72,575
of 248,573 outputs
Outputs of similar age from Diabetes
#59
of 133 outputs
Altmetric has tracked 30,202,275 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 10,844 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 10.2. This one has gotten more attention than average, scoring higher than 57% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 248,573 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.
We're also able to compare this research output to 133 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 54% of its contemporaries.
