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Journal of Neuroinflammation

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Open Access 01-12-2012 | Research

GLP-1 secretion by microglial cells and decreased CNS expression in obesity

Authors: Camilla Kappe, Linda M Tracy, Cesare Patrone, Kerstin Iverfeldt, Åke Sjöholm

Published in: Journal of Neuroinflammation | Issue 1/2012

Abstract

Background

Type 2 diabetes (T2D) is a strong risk factor for developing neurodegenerative pathologies. T2D patients have a deficiency in the intestinal incretin hormone GLP-1, which has been shown to exert neuroprotective and anti-inflammatory properties in the brain.

Methods

Here we investigate potential sources of GLP-1 in the CNS and the effect of diabetic conditions on the proglucagon mRNA expression in the CNS. The obese mouse model ob/ob, characterized by its high levels of free fatty acids, and the microglia cell line BV-2 were used as models. mRNA expression and protein secretion were analyzed by qPCR, immunofluorescence and ELISA.

Results

We show evidence for microglia as a central source of GLP-1 secretion. Furthermore, we observed that expression and secretion are stimulated by cAMP and dependent on microglial activation state. We also show that insulin-resistant conditions reduce the central mRNA expression of proglucagon.

Conclusion

The findings that microglial mRNA expression of proglucagon and GLP-1 protein expression are affected by high levels of free fatty acids and that both mRNA expression levels of proglucagon and secretion levels of GLP-1 are affected by inflammatory stimuli could be of pathogenic importance for the premature neurodegeneration and cognitive decline commonly seen in T2D patients, and they may also be harnessed to advantage in therapeutic efforts to prevent or treat such disorders.

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Title: GLP-1 secretion by microglial cells and decreased CNS expression in obesity
Authors: Camilla Kappe
Linda M Tracy
Cesare Patrone
Kerstin Iverfeldt
Åke Sjöholm
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2012
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-9-276

Keynote webinar | Spotlight on medication adherence

Springer Medicine

GLP-1 secretion by microglial cells and decreased CNS expression in obesity

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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