The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Irisin improves fatty acid oxidation and glucose utilization in type 2 diabetes by regulating the AMPK signaling pathway
Abstract
Background/objectives It has been reported that irisin regulated exercise-mediated adipocyte browning; however, the systematical effects of irisin on the metabolism of glucose and lipid in diabetes are largely unknown. In the present study, we investigated the role and underlying mechanism of irisin in glucose utilization and lipid metabolism in diabetic mice.Methods A mouse model of diabetes was established by feeding C57BL/6 mice with high-fat diet. The diabetic mice were then treated with irisin. To mimic type 2 diabetes in vitro, myocytes and hepatocytes were cultured in a medium of high glucose and high fat. Glucose uptake, fatty acid oxidation and the expression of related protein were evaluated.Results Irisin improved glucose tolerance and glucose uptake as evidenced by increased (18)F-FDG accumulation and GLUT4 translocation in diabetic skeletal muscle. Irisin also increased glucose uptake in myocytes cultured in high glucose/high fatty acid medium. In contrast, irisin reduced the expression of PEPCK and G6Pase, which are involved in gluconeogenesis, in diabetic liver. Consistently, irisin reduced fat weight and serum total cholesterol and triglyceride levels in diabetic mice, but increased acetyl coenzyme A carboxylase-β phosphorylation in muscle tissue and uncoupling protein 1 expression in fat tissue. In addition, irisin increased the oxidation of fatty acid in myocytes. Knockdown of the adenosine monophosphate (AMP)-activated protein kinase (AMPK) attenuated the effects of irisin on glucose uptake and fatty acid β-oxidation in myocytes. Similarly, inhibition of AMPK by a specific inhibitor reduced the effects of irisin on PEPCK and G6Pase expression in hepatocytes.Conclusions Our results suggest that irisin has an essential role in glucose utilization and lipid metabolism, and irisin is a promising pharmacological target for the treatment of diabetes and its complications.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In SkM, after physical activity, irisin induced downstream activation of glucose and FFA uptake and oxidation [62].”
In the citing paper
“Exercise-inducible myokines, such as irisin [62,63], IL-6 [76,77], IL-15 [91,126], BAIBA [111], and METRNL [100], as well as the osteokine OCN [71] have been shown to directly stimulate oxidative metabolism in autocrine and endocrine ways, respectively (1).”
In the citing paper
“Other studies have reported effects of irisin on body fat reduction through other mechanisms, such as improved glucose tolerance and lipid oxidation via phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA-carboxylase [52, 53].”
Citations
Cites
Insulin signalling and the regulation of glucose and lipid metabolism
Saltiel, A. R., & Kahn, C. R. (2001) · Nature · doi:10.1038/414799a · Cited by 5,326
Paradoxical Decrease of an Adipose-Specific Protein, Adiponectin, in Obesity
Arita, Y., Kihara, S., Ouchi, N., Takahashi, M., Maeda, K., Miyagawa, J.-I., Hotta, K., Shimomura, I., Nakamura, T., Miyaoka, K., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0255 · Cited by 4,856
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
Obesity and insulin resistance
Kahn, B. B., & Flier, J. S. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10842 · Cited by 3,345
THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?
Hardie, D. G., Carling, D., & Carlson, M. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.821 · Cited by 1,440
Petrovic, N., Walden, T. B., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.053942 · Cited by 1,263
The AMP-activated protein kinase cascade – a unifying system for energy control
Carling, D. (2003) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2003.11.005 · Cited by 1,133
Merrill, G. F., Kurth, E. J., Hardie, D. G., & Winder, W. W. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.6.e1107 · Cited by 1,048
AMPK: An Emerging Drug Target for Diabetes and the Metabolic Syndrome
Zhang, B. B., Zhou, G., & Li, C. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.012 · Cited by 1,042
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
Cited by
Sorted by citations
Kalinkovich, A., & Livshits, G. (2017) · Ageing Research Reviews · doi:10.1016/j.arr.2016.09.008 · Cited by 882
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
Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases
Demine, S., Renard, P., & Arnould, T. (2019) · Cells · doi:10.3390/cells8080795 · Cited by 476
PGC-1α as a Pivotal Factor in Lipid and Metabolic Regulation
Cheng, C., Ku, H., & Lin, H. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113447 · Cited by 450
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 432
“However, patients with obesity or T2DM show higher levels of FFAs that lead to insulin resistance [4], which further contributes to ED, a pivotal step in the initiation and progression of atherosclerosis [148].”
BackgroundInfluential
Metadata
- Authors
- Xin, C., Liu, J., Zhang, J., Zhu, D., Wang, H., Xiong, L., Lee, Y., Ye, J., Lian, K., Xu, C., Zhang, L., Wang, Q., Liu, Y., & Tao, L.
- Affiliations
- Second Artillery General Hospital of Chinese People's Liberation Army (CN)
- Xijing Hospital (CN)
- Corresponding author
- Liu, Y
- Tao, L
- Venue
- International Journal of Obesity
- Published
- 2015-09-25
- Volume
- 40
- Issue
- 3
- Pages
- 443-451
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W1923336662
- Cited by
- 248
- References
- 44
- Citations by year
- 2026: 16 · 2025: 18 · 2024: 24 · 2023: 26 · 2022: 28 · 2021: 32 · 2020: 29 · 2019: 19 · 2018: 22 · 2017: 21 · 2016: 12 · 2015: 1
- FWCI
- 14.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- irisin, type 2 diabetes, AMPK signaling, fatty acid oxidation, glucose utilization, glucose uptake, GLUT4 translocation, skeletal muscle, gluconeogenesis, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, hepatic glucose metabolism, lipid metabolism, ACACB, UCP1, high-fat diet, glucose tolerance
- MeSH terms
- Animals, Blood Glucose, Diabetes Mellitus, Experimental, Disease Models, Animal, Fatty Acids, Fibronectins, Glucose, Male, Mice, Inbred C57BL, Oxidation-Reduction, Phosphorylation, Signal Transduction, Muscle, Skeletal, Lipid Metabolism, Glucose Transporter Type 4, Mice, AMP-Activated Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
