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The Fractalkine/CX3CR1 System Regulates β Cell Function and Insulin Secretion
Open accessAbstract
Here, we demonstrate that the fractalkine (FKN)/CX3CR1 system represents a regulatory mechanism for pancreatic islet β cell function and insulin secretion. CX3CR1 knockout (KO) mice exhibited a marked defect in glucose and GLP1-stimulated insulin secretion, and this defect was also observed in vitro in isolated islets from CX3CR1 KO mice. In vivo administration of FKN improved glucose tolerance with an increase in insulin secretion. In vitro treatment of islets with FKN increased intracellular Ca(2+) and potentiated insulin secretion in both mouse and human islets. The KO islets exhibited reduced expression of a set of genes necessary for the fully functional, differentiated β cell state, whereas treatment of wild-type (WT) islets with FKN led to increased expression of these genes. Lastly, expression of FKN in islets was decreased by aging and high-fat diet/obesity, suggesting that decreased FKN/CX3CR1 signaling could be a mechanism underlying β cell dysfunction in type 2 diabetes.
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“Limited human data show that an acute exercise bout increases plasma and muscle expression levels of fractalkine (encoded by CX3CL1)70, which is a chemokine that favourably regulates glucose-stimulated insulin secretion by enhancing β-cell function114.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [114]
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“Furthermore, other ligand/receptor systems previously implicated in immune cell chemotaxis such as fractalkine/CX3CR1 and SDF1/CXCR4, can increase GSIS and/or b-cell proliferation (Kayali et al., 2012; Lee et al., 2013; Yano et al., 2007).”
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Oh, D. Y., Walenta, E., Akiyama, T. E., Lagakos, W., Lackey, D. E., Pessentheiner, A. R., Šášik, R., Hah, N., Chi, T. J., Cox, J. M., et al. (2014) · Nature Medicine · doi:10.1038/nm.3614 · Cited by 397
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“…process, and acute islet inflammation may be beneficial for the maintenance of islet function in the normal state (Banaei-Bouchareb et al. 2004; Geutskens et al. 2005; Yano et al. 2007; Kayali et al. 2012; Lee et al. 2013; Dror et al. 2017; Burke et al. 2018; Riopel et al. 2018; Ying et al. 2019).”
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Metadata
- Authors
- Lee, Y. S., Morinaga, H., Kim, J. J., Lagakos, W., Taylor, S., Keshwani, M., Perkins, G., Dong, H., Kayali, A. G., Sweet, I. R., & Olefsky, J.
- Affiliations
- University of California San Diego (US)
- University of Washington (US)
- Corresponding author
- Olefsky, Jerrold
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 153
- Issue
- 2
- Pages
- 413-425
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3717389
- OpenAlex
- W1965673611
- Cited by
- 141
- References
- 44
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 7 · 2022: 17 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 15 · 2017: 17 · 2016: 11 · 2015: 12 · 2014: 14 · 2013: 2
- FWCI
- 12.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK063491, DK 074868, DK 033651, T32DK007494, R37DK033651, R01DK101395, P01DK074868, R01DK033651, P30DK017047, P30DK063491)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (U54HD012303)
- 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 › Genetics › Diabetes and associated disorders
- Keywords
- fractalkine, CX3CR1, beta-cell function, insulin secretion, pancreatic islets, glucose tolerance, glucagon-like peptide-1, intracellular calcium, beta cell differentiation, aging, high-fat diet, obesity, type 2 diabetes, chemokine signaling
- MeSH terms
- CX3C Chemokine Receptor 1, Insulin Secretion, Adult, Aging, Animals, Cadaver, Glucose, Humans, Hyperglycemia, Insulin, Islets of Langerhans, Male, Mice, Inbred C57BL, Middle Aged, Signal Transduction, Gene Expression, Mice, Knockout, Receptors, Chemokine, Insulin-Secreting Cells, Mice, Chemokine CX3CL1, Diet, High-Fat
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