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Selected Publication:
Uhlig, M.
Evaluation of nephroprotective effects of glucagon-like peptide 1 receptor in renal ischemia reperfusion injury
Humanmedizin; [ Diplomarbeit ] Medical University of Graz; 2019. pp. 93
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- Authors Med Uni Graz:
- Advisor:
- Eller Kathrin
- Eller Philipp
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- Abstract:
- Liraglutide affects various mechanisms that are decisive in IRI like the RAAS, reactive oxygen species and inflammation (155). Therefore we aimed to test the hypothesis that liraglutide exhibits a nephroprotektive effect in a murine model of renal IRI. Here, we followed two approaches: first, we compared the outcome of GLP-1R -/- mice with wild-type mice, and secondly wild-type mice with liraglutide treatment (200μg/kgBW/d starting 7 days prior to surgery) versus vehicle. We hypothesized an improved outcome of wild-type compared to the knock-out mice and a further improvement with the administration of liraglutide as a protective agonist. The results of this study suggest a protective effect of GLP-1R activation in renal IRI. There was a significant increase in the retention parameters urea (p = 0.043) and creatinine (p = 0.0473) in GLP-1R deficient mice, on the other hand there was an alleviation of renal IRI when the GLP-1 receptor was activated. In animals pretreated with liraglutide we observed significantly decreased serum urea (p = 0.0149) and BUN levels (p = 0.03). Unfortunately, this improvement in outcomes was not directly reflected in the histology, although a significantly higher number of macrophages (p = 0.0286) was detected in mice treated with liraglutide. The following L-Arg stain showed a non-significant trend (p = 0.1111) towards the benefit of the M2 phenotype, which at least suggests that the majority of the additional macrophages might have been of the M2/repair type In summary, the absence of the GLP-1R aggravated the impairment of kidney functions in renal IRI, as well as the activation of the GLP-1R by liraglutide ameliorated the AKI and preserved kidney functions. Therefore, we conclude that liraglutide has a reno-protective effect in mice subjected to renal IRI. Not only does this further elucidate the underlying mechanism of the improved renal outcome that was seen in large-scale clinical trials, but also reveals the potential that Liraglutide might have for the treatment of AKI.