ISSN:
2379-3708
Content:
The increased formation of methylglyoxal (MG) under hyperglycemia is associated with the development of microvascular complications in patients with diabetes mellitus; however, the effects of elevated MG levels in vivo are poorly understood. In zebrafish, a transient knockdown of glyoxalase 1, the main MG detoxifying system, led to the elevation of endogenous MG levels and blood vessel alterations. To evaluate effects of a permanent knockout of glyoxalase 1 in vivo, glo1–/– zebrafish mutants were generated using CRISPR/Cas9. In addition, a diet-induced–obesity zebrafish model was used to analyze glo1–/– zebrafish under high nutrient intake. Glo1–/– zebrafish survived until adulthood without growth deficit and showed increased tissue MG concentrations. Impaired glucose tolerance developed in adult glo1–/– zebrafish and was indicated by increased postprandial blood glucose levels and postprandial S6 kinase activation. Challenged by an overfeeding period, fasting blood glucose levels in glo1–/– zebrafish were increased which translated into retinal blood vessel alterations. Thus, the data have identified a defective MG detoxification as a metabolic prerequisite and glyoxalase 1 alterations as a genetic susceptibility to the development of type 2 diabetes mellitus under high nutrition intake.
Note:
Published June 20, 2019
,
Gesehen am 06.11.2019
In:
JCI insight, Ann Arbor, Michigan : JCI Insight, 2016, 4(2019,12) Artikel-Nummer e126154, 17 Seiten, 2379-3708
In:
volume:4
In:
year:2019
In:
number:12
Language:
English
DOI:
10.1172/jci.insight.126154
URL:
https://insight.jci.org/articles/view/126154
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