Email updates

Keep up to date with the latest news and content from JNI and BioMed Central.

Open Access Highly Accessed Research

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

Camilla Kappe1, Linda M Tracy2, Cesare Patrone1, Kerstin Iverfeldt2* and Åke Sjöholm1*

Author Affiliations

1 Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm, 11883, Sweden

2 Department of Neurochemistry, Stockholm University, Stockholm, 10691, Sweden

For all author emails, please log on.

Journal of Neuroinflammation 2012, 9:276  doi:10.1186/1742-2094-9-276

Published: 23 December 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.

Keywords:
Glucagon-like peptide-1; Microglia; Neuroinflammation; Neuroprotection; Proglucagon