The effect of GLP-1 receptor agonist lixisenatide on experimental diabetic retinopathy.
Rats
Animals
Diabetic Retinopathy
/ drug therapy
Diabetes Mellitus, Type 2
/ metabolism
Hypoglycemic Agents
/ pharmacology
Glucagon-Like Peptide-1 Receptor
/ agonists
Caenorhabditis elegans
Chromatography, Liquid
Rats, Wistar
Diabetes Mellitus, Experimental
/ drug therapy
Tandem Mass Spectrometry
Antioxidants
/ pharmacology
Glucose
Diabetic retinopathy
Ets2
GLP-1RA
Lixisenatide
Neurovascular unit
ROS
Journal
Acta diabetologica
ISSN: 1432-5233
Titre abrégé: Acta Diabetol
Pays: Germany
ID NLM: 9200299
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
27
01
2023
accepted:
10
06
2023
medline:
4
10
2023
pubmed:
10
7
2023
entrez:
9
7
2023
Statut:
ppublish
Résumé
Glucagon-like peptide-1 receptor agonists are effective treatments for type 2 diabetes, effectively lowering glucose without weight gain and with low risk for hypoglycemia. However, their influence on the retinal neurovascular unit remains unclear. In this study, we analyzed the effects of the GLP-1 RA lixisenatide on diabetic retinopathy. Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats, acellular capillaries and pericytes (quantitative retinal morphometry), neuroretinal function (mfERG), macroglia (GFAP western blot) and microglia (immunohistochemistry) quantification, methylglyoxal (LC-MS/MS) and retinal gene expressions (RNA-sequencing) were determined. The antioxidant properties of lixisenatide were tested in C. elegans. Lixisenatide had no effect on glucose metabolism. Lixisenatide preserved the retinal vasculature and neuroretinal function. The macro- and microglial activation was mitigated. Lixisenatide normalized some gene expression changes in diabetic animals to control levels. Ets2 was identified as a regulator of inflammatory genes. In C. elegans, lixisenatide showed the antioxidative property. Our data suggest that lixisenatide has a protective effect on the diabetic retina, most likely due to a combination of neuroprotective, anti-inflammatory and antioxidative effects of lixisenatide on the neurovascular unit.
Identifiants
pubmed: 37423944
doi: 10.1007/s00592-023-02135-7
pii: 10.1007/s00592-023-02135-7
pmc: PMC10520173
doi:
Substances chimiques
lixisenatide
74O62BB01U
Hypoglycemic Agents
0
Glucagon-Like Peptide-1 Receptor
0
Antioxidants
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1551-1565Informations de copyright
© 2023. The Author(s).
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