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

Journal of neuroinflammation (2012-12-25)
Camilla Kappe, Linda M Tracy, Cesare Patrone, Kerstin Iverfeldt, Åke Sjöholm
ABSTRACT

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. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
灰链霉菌来源几丁质酶, lyophilized powder (essentially salt free), ≥200 units/g solid
Sigma-Aldrich
棕榈酸钠, ≥98.5%
Sigma-Aldrich
壳质酶 来源于绿色木霉, lyophilized powder, ≥600 units/g solid
Sigma-Aldrich
L-精氨酸酶 来源于牛肝脏, Protein ≥70 % by biuret, powder