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FFAR3 modulates insulin secretion and global gene expression in mouse islets
Open accessAbstract
The short chain fatty acid (SCFA) receptor (free fatty acid receptor-3; FFAR3) is expressed in pancreatic β cells; however, its role in insulin secretion is not clearly defined. Here, we examined the role of FFAR3 in insulin secretion. Using islets from global knockout FFAR3 (Ffar3(-/-)) mice, we explored the role of FFAR3 and ligand-induced FFAR3 signaling on glucose stimulated insulin secretion. RNA sequencing was also performed to gain greater insight into the impact of FFAR3 deletion on the islet transcriptome. First exploring insulin secretion, it was determined that Ffar3(-/-) islets secrete more insulin in a glucose-dependent manner as compared to wildtype (WT) islets. Next, exploring its primary endogenous ligand, propionate, and a specific agonist for FFAR3, signaling by FFAR3 inhibited glucose-dependent insulin secretion, which occurred through a Gαi/o pathway. To help understand these results, transcriptome analyses by RNA-sequencing of Ffar3(-/-) and WT islets observed multiple genes with well-known roles in islet biology to be altered by genetic knockout of FFAR3. Our data shows that FFAR3 signaling mediates glucose stimulated insulin secretion through Gαi/o sensitive pathway. Future studies are needed to more rigorously define the role of FFAR3 by in vivo approaches.
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“The loss of FFAR3, encoding an insulin secretion inhibitor37, may explain why fruit bats secrete substantially more insulin than other mammals38.”
From A genomics approach reveals insights into the importance of gene losses for mammalian adaptations (2018) · cites this paper as [37]
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The Fractalkine/CX3CR1 System Regulates β Cell Function and Insulin Secretion
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“While genetic GPCR knockout models have been observed to impact the expression of other genes and in particular genes important in islet biology [26, 27], the impact of these additional genetic changes on functional outcomes such as GSIS needs to be”
BackgroundPropionate inhibits glucose‐induced insulin secretion in isolated rat pancreatic islets
Ximenes, H. M. A., Hirata, A. E., Rocha, M. S., Curi, R., & Carpinelli, A. R. (2007) · Cell Biochemistry and Function · doi:10.1002/cbf.1297 · Cited by 58 · cited 2×
“One study observed that propionate inhibits GSIS [11] and another study observed that butyrate enhances GSIS [12].”
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Sorted by citations
A genomics approach reveals insights into the importance of gene losses for mammalian adaptations
Sharma, V., Hecker, N., Roscito, J. G., Foerster, L., Langer, B. E., & Hiller, M. (2018) · Nature Communications · doi:10.1038/s41467-018-03667-1 · Cited by 237
The dynamic plasticity of insulin production in β-cells
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Metadata
- Authors
- Priyadarshini, M., & Layden, B. T.
- Affiliations
- Northwestern University (US)
- Corresponding author
- Layden, Brian T
- Venue
- Islets
- Publisher
- Informa UK Limited
- Published
- 2015-03-04
- Volume
- 7
- Issue
- 2
- Pages
- e1045182
- ISSN
- 1938-2014 (ISSN-L)
- 1938-2022
- PMC
- PMC4878265
- OpenAlex
- W2279049687
- Cited by
- 79
- References
- 6
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 5 · 2023: 8 · 2022: 8 · 2021: 15 · 2020: 8 · 2019: 2 · 2018: 4 · 2017: 3 · 2016: 9 · 2015: 3
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Islets (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2 BX001587)
- American Heart Association (15POST22410016)
- Northwestern University
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- FFAR3, insulin secretion, glucose-stimulated insulin secretion, pancreatic beta cells, pancreatic islets, propionate, islet transcriptome, short-chain fatty acid receptors
- MeSH terms
- Insulin Secretion, Animals, Insulin, Male, Mice, Inbred C57BL, Signal Transduction, Gene Expression, Mice, Knockout, Receptors, G-Protein-Coupled, Insulin-Secreting Cells, Mice, Transcriptome, Real-Time Polymerase Chain Reaction
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