The DOI matches its Crossref record; 34 of the 35 references it cites were found in a registry or an index.
Fibroblast Growth Factor 21 Controls Glycemia via Regulation of Hepatic Glucose Flux and Insulin Sensitivity
Open accessAbstract
Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator shown to improve glycemic control. However, the molecular and functional mechanisms underlying FGF21-mediated improvements in glycemic control are not completely understood. We examined FGF21 effects on insulin sensitivity and glucose fluxes upon chronic (daily injection for 8 d) and acute (6 h infusion) administration in ob/+ and ob/ob mice. Results show that chronic FGF21 ameliorated fasting hyperglycemia in ob/ob mice via increased glucose disposal and improved hepatic insulin sensitivity. Acute FGF21 suppressed hepatic glucose production, increased liver glycogen, lowered glucagon, and improved glucose clearance in ob/+ mice. These effects were blunted in ob/ob mice. Neither chronic nor acute FGF21 altered skeletal muscle or adipose tissue glucose uptake in either genotype. In conclusion, FGF21 has potent glycemic effects caused by hepatic changes in glucose flux and improved insulin sensitivity. Thus, these studies define mechanisms underlying anti-hyperglycemic actions of FGF21 and support its therapeutic potential.
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“This decrease in plasma glucose levels occurs primarily through increased peripheral glucose disposal41,56,65, although decreases in hepatic glucose production have also been observed66.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [66]
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FGF-21 as a novel metabolic regulator
Kharitonenkov, A., Shiyanova, T. L., Koester, A., Ford, A. M., Micanovic, R., Galbreath, E. J., Sandusky, G. E., Hammond, L. J., Moyers, J. S., Owens, R. A., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23606 · Cited by 2,125
Self-citationInagaki, T., Dutchak, P., Zhao, G., Ding, X., Gautron, L., Parameswara, V., Li, Y., Goetz, R., Mohammadi, M., Esser, V., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.003 · Cited by 1,504
Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
Xu, J., Lloyd, D. J., Hale, C., Stanislaus, S., Chen, M., Sivits, G., Vonderfecht, S., Hecht, R., Li, Y.-S., Lindberg, R. A., et al. (2009) · Diabetes · doi:10.2337/db08-0392 · Cited by 1,151
Fibroblast Growth Factor 21 Corrects Obesity in Mice
Coskun, T., Bina, H. A., Schneider, M. A., Dunbar, J. D., Hu, C. C., Chen, Y., Moller, D. E., & Kharitonenkov, A. (2008) · Endocrinology · doi:10.1210/en.2008-0816 · Cited by 1,031
Self-citationZhang, X., Yeung, D. C. Y., Karpisek, M., Stejskal, D., Zhou, Z.-G., Liu, F., Wong, R. L. C., Chow, W.-S., Tso, A. W. K., Lam, K. S. L., et al. (2008) · Diabetes · doi:10.2337/db07-1476 · Cited by 908
The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21
Kharitonenkov, A., Wroblewski, V. J., Koester, A., Chen, Y.-F., Clutinger, C. K., Tigno, X. T., Hansen, B. C., Shanafelt, A. B., & Etgen, G. J. (2007) · Endocrinology · doi:10.1210/en.2006-1168 · Cited by 738
Self-citationβKlotho is required for metabolic activity of fibroblast growth factor 21
Ogawa, Y., Kurosu, H., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Goetz, R., Eliseenkova, A. V., Mohammadi, M., & Kuro-o, M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0701600104 · Cited by 617
Viollet, B., Foretz, M., Guigas, B., Horman, S., Dentin, R., Bertrand, L., Hue, L., & Andréelli, F. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.108506 · Cited by 543
Wente, W., Efanov, A. M., Brenner, M. B., Kharitonenkov, A., Koster, A. M., Sandusky, G. E., Sewing, S., Treinies, I., Zitzer, H., & Gromada, J. (2006) · Diabetes · doi:10.2337/db05-1435 · Cited by 497
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FGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478
Self-citationExercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis
He, C., Bassik, M. C., Moresi, V., Sun, K., Wei, Y., Zou, Z., An, Z., Loh, J., Fisher, J., Sun, Q., et al. (2012) · Nature · doi:10.1038/nature10758 · Cited by 1,136
Understanding the Physiology of FGF21
Fisher, F. M., & Maratos-Flier, E. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105339 · Cited by 912
The effects of LY2405319, an FGF21 analog, in obese human subjects with type 2 diabetes
Gaich, G., Chien, J. Y., Fu, H., Glass, L. C., Deeg, M. A., Holland, W. L., Kharitonenkov, A., Bumol, T., Schilske, H. K., & Moller, D. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.08.005 · Cited by 885
Self-citationReceptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin
Holland, W. L., Miller, R. A., Wang, Z. V., Sun, K., Barth, B. M., Bui, H. H., Davis, K. E., Bikman, B. T., Halberg, N., Rutkowski, J. M., et al. (2011) · Nature Medicine · doi:10.1038/nm.2277 · Cited by 892
Metadata
- Authors
- Berglund, E. D., Li, C. Y., Bina, H. A., Lynes, S. E., Michael, M. D., Shanafelt, A. B., Kharitonenkov, A., & Wasserman, D. H.
- Affiliations
- National Institutes of Health (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Berglund, Eric D.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2009-05-21
- Volume
- 150
- Issue
- 9
- Pages
- 4084-4093
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- PMC
- PMC2736088
- OpenAlex
- W1977516373
- Cited by
- 297
- References
- 35
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 15 · 2023: 18 · 2022: 18 · 2021: 11 · 2020: 19 · 2019: 15 · 2018: 13 · 2017: 20 · 2016: 19 · 2015: 23 · 2014: 27 · 2013: 21 · 2012: 26
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Vanderbilt University
- National Institutes of Health (DK-59637, U24 DK59637)
- National Institute of Diabetes and Digestive and Kidney Diseases (U24DK59637, R01 DK-50277, T32DK07563, U24DK059637, R01DK050277, T32DK007563)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- FGF21, glycemic control, insulin sensitivity, hepatic glucose production, liver glycogen, glucagon, glucose clearance, fasting hyperglycemia, ob/ob mice, obesity, glucose disposal
- MeSH terms
- Animals, Blood Glucose, Fasting, Fibroblast Growth Factors, Glucagon, Insulin Resistance, Liver, Liver Glycogen, Male, Mice, Obese, Mice
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