GLP-1 secretion by microglial cells and decreased CNS expression in obesity
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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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GLP-1 is known to be produced in the brain and has many functions including neuroprotection.
“GLP-1 is known to be produced in the brain [79] and has many functions including neuroprotection [80–82].”
From Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control (2016) · cites this paper as [79]
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- Authors
- Kappe, C., Tracy, L. M., Patrone, C., Iverfeldt, K., & Sjöholm, Å.
- Affiliations
- Stockholm University (SE)
- Karolinska Institutet (SE)
- Corresponding author
- Tracy, Linda M
- Iverfeldt, Kerstin
- Sjöholm, Åke
- Venue
- Journal of Neuroinflammation
- Published
- 2012-12
- Volume
- 9
- Issue
- 1
- Pages
- 276-276
- ISSN
- 1742-2094 (ISSN-L)
- PMC
- PMC3546916
- OpenAlex
- W2112292567
- Cited by
- 107
- References
- 32
- Citations by year
- 2026: 6 · 2025: 10 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 7 · 2020: 11 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 9 · 2015: 7 · 2014: 3 · 2013: 3
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Journal of Neuroinflammation (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Gun och Bertil Stohnes Stiftelse
- AFA Försäkring
- Karolinska Institutet
- Stockholms Läns Landsting
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- glucagon-like peptide-1, proglucagon, microglia, obesity, type 2 diabetes, neurodegeneration, insulin resistance, free fatty acids, cAMP signaling, microglial activation, neuroinflammation, cognitive decline
- MeSH terms
- Cyclic AMP, Animals, Arginase, Cell Line, Transformed, Central Nervous System, Chitinases, Disease Models, Animal, Gene Expression Regulation, Insulin Resistance, Male, Mice, Inbred C57BL, Mice, Obese, Obesity, Palmitates, Plant Proteins, Polysaccharides, RNA, Messenger, Transfection, Tumor Necrosis Factor-alpha, Microglia, Statistics, Nonparametric, CD11b Antigen, Mice, Glucagon-Like Peptide 1, Proglucagon
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