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Horm Metab Res 2016; 48(01): 70-75
DOI: 10.1055/s-0035-1549876
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Protective Effects of Liraglutide and Linagliptin in C. elegans as a New Model for Glucose-Induced Neurodegeneration

K. Wongchai
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
A. Schlotterer
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
J. Lin
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
P. M. Humpert
2   Stoffwechselzentrum Rhein-Pfalz, Innere Medizin, Endocrinologie & Diabetologie, Mannheim, Germany
,
T. Klein
3   Boehringer Mannheim Pharma GmbH & Co. KG., Metabolic Diseases, Biberach an der Riß, Germany
,
H.-P. Hammes
1   5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
,
M. Morcos
2   Stoffwechselzentrum Rhein-Pfalz, Innere Medizin, Endocrinologie & Diabetologie, Mannheim, Germany
› Author Affiliations
Further Information

Publication History

received 08 December 2014

accepted 31 March 2015

Publication Date:
07 May 2015 (online)

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Abstract

Liraglutide and linagliptin are novel drugs for the treatment of diabetes. Antioxidative and neuroprotective effects have been described for both compounds. However, it is not yet known, whether these mechanisms are also protective against diabetic retinal neurodegeneration. We assessed the antioxidative and neuroprotective capabilities of liraglutide and linagliptin as well as the signaling pathways involved, by using C. elegans as a model for glucose-induced neurodegeneration. C. elegans were cultivated under conditions, which mimic clinical hyperglycemia, and treated with 160 μmol/l liraglutide or 13 μmol/l linagliptin. Oxidative stress was reduced by 29 or 78% and methylglyoxal-derived advanced glycation endproducts (AGEs) by 33 or 22%, respectively. This resulted in an improved neuronal function by 42 or 60% and an extended mean lifespan by 9 or 11%, respectively. Antioxidative and AGE reducing effects of liraglutide and linagliptin were not dependent on v-akt murine thymoma viral oncogene homologue 1/forkhead box O1 (AKT1/FOXO). Neuroprotection by liraglutide was AKT1/FOXO dependent, yet AKT1/FOXO independent upon linagliptin treatment. Both liraglutide and linagliptin exert neuroprotective effects in an experimental model for glucose-induced neurodegeneration, however, the signaling pathways differ in the present study. Further pharmacological intervention with these pathways may help to delay the clinical onset of diabetic retinopathy by preserving neuronal integrity.

Key words

GLP-1 - DPP-4 - neuroprotective effects - diabetic complications
 

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