The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes
Abstract
Increased glucose production and reduced hepatic glycogen storage contribute to metabolic abnormalities in diabetes. Irisin, a newly identified myokine, induces the browning of white adipose tissue, but its effects on gluconeogenesis and glycogenesis are unknown. In the present study, we investigated the effects and underlying mechanisms of irisin on gluconeogenesis and glycogenesis in hepatocytes with insulin resistance, and its therapeutic role in type 2 diabetic mice. Insulin resistance was induced by glucosamine (GlcN) or palmitate in human hepatocellular carcinoma (HepG2) cells and mouse primary hepatocytes. Type 2 diabetes was induced by streptozotocin/high-fat diet (STZ/HFD) in mice. In HepG2 cells, irisin ameliorated the GlcN-induced increases in glucose production, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) expression, and glycogen synthase (GS) phosphorylation; it prevented GlcN-induced decreases in glycogen content and the phosphoinositide 3-kinase (PI3K) p110α subunit level, and the phosphorylation of Akt/protein kinase B, forkhead box transcription factor O1 (FOXO1) and glycogen synthase kinase-3 (GSK3). These effects of irisin were abolished by the inhibition of PI3K or Akt. The effects of irisin were confirmed in mouse primary hepatocytes with GlcN-induced insulin resistance and in human HepG2 cells with palmitate-induced insulin resistance. In diabetic mice, persistent subcutaneous perfusion of irisin improved the insulin sensitivity, reduced fasting blood glucose, increased GSK3 and Akt phosphorylation, glycogen content and irisin level, and suppressed GS phosphorylation and PEPCK and G6Pase expression in the liver. Irisin improves glucose homoeostasis by reducing gluconeogenesis via PI3K/Akt/FOXO1-mediated PEPCK and G6Pase down-regulation and increasing glycogenesis via PI3K/Akt/GSK3-mediated GS activation. Irisin may be regarded as a novel therapeutic strategy for insulin resistance and type 2 diabetes.
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Cites
A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., et al. (2012) · Nature · doi:10.1038/nature10777 · Cited by 4,810
Srinivasan, K., Viswanad, B., Asrat, L., Kaul, C. L., & Ramarao, P. (2005) · Pharmacological Research · doi:10.1016/j.phrs.2005.05.004 · Cited by 1,874
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821
Cohen, P., & Frame, S. (2001) · Nature Reviews Molecular Cell Biology · doi:10.1038/35096075 · Cited by 1,478
The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes
Perry, R. J., Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2014) · Nature · doi:10.1038/nature13478 · Cited by 1,136
Huh, J. Y., Panagiotou, G., Mougios, V., Brinkoetter, M., Vamvini, M. T., Schneider, B. E., & Mantzoros, C. S. (2012) · Metabolism · doi:10.1016/j.metabol.2012.09.002 · Cited by 1,040
A new rat model of type 2 diabetes: The fat-fed, streptozotocin-treated rat
Reed, M. J., Meszaros, K., Entes, L. J., Claypool, M. D., Pinkett, J. G., Gadbois, T. M., & Reaven, G. M. (2000) · Metabolism · doi:10.1053/meta.2000.17721 · Cited by 848
SIRT1 Improves Insulin Sensitivity under Insulin-Resistant Conditions by Repressing PTP1B
Sun, C., Zhang, F., Ge, X., Yan, T., Chen, X., Shi, X., & Zhai, Q. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.08.014 · Cited by 766
FROM MICE TO MEN: Insights into the Insulin Resistance Syndromes
Biddinger, S. B., & Kahn, C. R. (2006) · Annual Review of Physiology · doi:10.1146/annurev.physiol.68.040104.124723 · Cited by 706
Zhang, M., Lv, X.-Y., Li, J., Xu, Z.-G., & Chen, L. (2008) · Journal of Diabetes Research · doi:10.1155/2008/704045 · Cited by 667
Cited by
The PI3K/AKT Pathway in Obesity and Type 2 Diabetes
Huang, X., Liu, G., Guo, J., & Su, Z. (2018) · International Journal of Biological Sciences · doi:10.7150/ijbs.27173 · Cited by 1,673
Physiology and role of irisin in glucose homeostasis
Perakakis, N., Triantafyllou, G. A., Fernández-Real, J. M., Huh, J. Y., Park, K. H., Seufert, J., & Mantzoros, C. S. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.221 · Cited by 621
PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation
Cheng, C.-F., Ku, H.-C., & Lin, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113447 · Cited by 437
Cell-cell communication: New insights and clinical implications
Su, J., Song, Y., Zhu, Z., Huang, X., Fan, J., Qiao, J., & Mao, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01888-z · Cited by 433
Role of free fatty acids in endothelial dysfunction
Ghosh, A., Gao, L., Thakur, A., Siu, P. M., & Lai, C. W. K. (2017) · Journal of Biomedical Science · doi:10.1186/s12929-017-0357-5 · Cited by 414
Metadata
- Authors
- Liu, T.-Y., Shi, C.-X., Gao, R., Sun, H.-J., Xiong, X.-Q., Ding, L., Chen, Q., Li, Y.-H., Wang, J.-J., Kang, Y.-M., & Zhu, G.-Q.
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2015-08-19
- Volume
- 129
- Issue
- 10
- Pages
- 839-850
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W1962787573
- Cited by
- 370
- References
- 43
- FWCI
- 8.11
- Type
- journal article
- Language
- en
- Open access
- closed
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- Liu, T.-Y., Shi, C.-X., Gao, R., Sun, H.-J., Xiong, X.-Q., Ding, L., Chen, Q., Li, Y.-H., Wang, J.-J., Kang, Y.-M., & Zhu, G.-Q. (2015). Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clinical Science. https://doi.org/10.1042/cs20150009
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