The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Cellular Mechanisms by Which FGF21 Improves Insulin Sensitivity in Male Mice
Open accessAbstract
Fibroblast growth factor 21 (FGF21) is a potent regulator of glucose and lipid metabolism and is currently being pursued as a therapeutic agent for insulin resistance and type 2 diabetes. However, the cellular mechanisms by which FGF21 modifies insulin action in vivo are unclear. To address this question, we assessed insulin action in regular chow– and high-fat diet (HFD)–fed wild-type mice chronically infused with FGF21 or vehicle. Here, we show that FGF21 administration results in improvements in both hepatic and peripheral insulin sensitivity in both regular chow– and HFD-fed mice. This improvement in insulin responsiveness in FGF21-treated HFD-fed mice was associated with decreased hepatocellular and myocellular diacylglycerol content and reduced protein kinase Cϵ activation in liver and protein kinase Cθ in skeletal muscle. In contrast, there were no effects of FGF21 on liver or muscle ceramide content. These effects may be attributed, in part, to increased energy expenditure in the liver and white adipose tissue. Taken together, these data provide a mechanism by which FGF21 protects mice from lipid-induced liver and muscle insulin resistance and support its development as a novel therapy for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes.
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Nonalcoholic Fatty Liver Disease
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Cellular mechanisms of insulin resistance
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Self-citationFGF-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
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Self-citationHolland, W. L., Brozinick, J. T., Wang, L.-P., Hawkins, E. D., Sargent, K. M., Liu, Y., Narra, K., Hoehn, K. L., Knotts, T. A., Siesky, A., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.01.002 · Cited by 1,232
Fibroblast Growth Factor 21 Corrects Obesity in Mice
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Inhibition of Growth Hormone Signaling by the Fasting-Induced Hormone FGF21
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Cited by
Mechanisms of Insulin Action and Insulin Resistance
Petersen, M. C., & Shulman, G. I. (2018) · Physiological Reviews · doi:10.1152/physrev.00063.2017 · Cited by 3,028
Self-citationThe pathogenesis of insulin resistance: integrating signaling pathways and substrate flux
Samuel, V. T., & Shulman, G. I. (2016) · Journal of Clinical Investigation · doi:10.1172/jci77812 · Cited by 1,484
Self-citationEctopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease
Shulman, G. I. (2014) · New England Journal of Medicine · doi:10.1056/nejmra1011035 · Cited by 1,126
Self-citationUnderstanding 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
Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases
Samuel, V. T., & Shulman, G. I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.002 · Cited by 745
“The increases in energy expenditure are associatedwith a reduction in hepatic diacylglycerol content, decreased PKCε activation, and improved insulin signaling (Camporez et al., 2013).”
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Metadata
- Authors
- Camporez, J. P. G., Jornayvaz, F. R., Petersen, M. C., Pesta, D., Guigni, B. A., Serr, J., Zhang, D., Kahn, M., Samuel, V. T., Jurczak, M. J., & Shulman, G. I.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2013-06-13
- Volume
- 154
- Issue
- 9
- Pages
- 3099-3109
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1969706853
- Cited by
- 228
- References
- 17
- FWCI
- 7.93
- Type
- journal article
- Language
- en
- Open access
- bronze
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