alexa Exendin-4 Protects Neural Progenitor Cells from Glucolipoapoptosis | OMICS International | Abstract
ISSN: 2155-6156

Journal of Diabetes & Metabolism
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Research Article

Exendin-4 Protects Neural Progenitor Cells from Glucolipoapoptosis

Shiva Mansouri1*, Vladimer Darsalia1, Mohamed Eweida2, Mathias Lundberg1, David Nathanson1 and Cesare Patrone1

1Cerebrometabolic Research Unit, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden

2Södersjukhuset AB, Stockholm, Sweden

*Corresponding Author:
Shiva Mansouri
Department of Clinical Science and Education
Södersjukhuset, Internal Medicine
Karolinska Institutet
Sjukhusbacken 10, 118 83
Stockholm, Sweden
Tel: +46 8 6165040
Fax: +46 8 616 2933
E-mail: [email protected]

Received date: June 07, 2014; Accepted date: August 23, 2014; Published date: September 01, 2014

Citation: Mansouri S, Darsalia V, Eweida M, Lundberg M, Nathanson D, et al. (2014) Exendin-4 Protects Neural Progenitor Cells from Glucolipoapoptosis. J Diabetes Metab 5:409 doi: 10.4172/2155-6156.1000409

Copyright: © 2014 Mansouri S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Type 2 diabetic and obese patients are under high risk to prematurely develop neurological complications such as stroke and Alzheimer’s disease. Interestingly, type 2-diabetes impairs adult neurogenesis in rodent animal models and this impairment has been suggested to play a role in the brain complications of this disease. Recent work from us and others showed that the treatment with the Glucagon-Like Peptide 1 Receptor (GLP-1R) agonist Exendin-4 stimulates adult neurogenesis in rodents.

Based on these findings we have raised the hypothesis that Exendin-4 may counteract the detrimental effects induced by diabetes in neural stem/progenitor cells. The aim of this study was to investigate whether Exendin-4 protect neural progenitor cells from glucolipotoxicity and to analyse if the regulation of apoptosis may be involved in the Exendin-4 protecting effect. Murine neural progenitor cells were exposed to high palmitate and glucose, which characterize diabetic glucolipotoxicity, in presence/absence of Exendin-4. To determine whether neural progenitor cells proliferation was impacted by the Exendin-4 treatment, [3H] thymidine incorporation experiments were also performed. The expression of apoptosis key players, such as cleaved-caspase 3 and Bcl-2, were evaluated by western blotting. We show that Exendin-4 counteracts the impaired neural progenitor cell viability induced by glucolipotoxicity.

Cell proliferation was not influenced by the Exendin-4 treatment. The protective effect induced by Exendin-4 correlated with decreased apoptosis. In addition, the Exendin-4 protective effect was completely abolished by using the GLP- 1R antagonist Ex-9-39, indicating that the protective effect by Exendin-4 was GLP-1R-mediated. In conclusion, we show a direct survival effect of GLP-1R activation on neural progenitor cells challenged by diabetic-like conditions. The results support a potential therapeutic role of GLP-1R agonists, based on neurogenesis stimulation, for the treatment of the neurological complications in Type 2-diabetes and obesity.


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