Elevated Circulating Levels of Irisin and the Effect of Metformin Treatment in Women With Polycystic Ovary Syndrome
Abstract
CONTEXT: Polycystic ovary syndrome (PCOS) is an insulin resistance (IR) state, like obesity and type 2 diabetes mellitus (T2DM). Although previous studies have suggested a correlation between irisin and the metabolic parameters associated with obesity and T2DM, the results have been inconsistent. OBJECTIVE: Our objective was to (1) determine circulating irisin levels in women with PCOS and control subjects, (2) examine the relationship of irisin and conventional markers of insulin resistance, and (3) examine irisin changes with interventions modulating IR in PCOS women. PATIENTS AND DESIGN: This study was comprised of a series of cross-sectional and interventional studies of 178 PCOS and 123 healthy women from the general population and outpatients of the Internal Medicine Department at the Second Affiliated Hospital, Chongqing Medical University, China. Forty seven women with PCOS were randomly assigned to 6 months of oral metformin (850 mg bid). The oral glucose tolerance test (OGTT) and the euglycemic-hyperinsulinemic clamp (EHC) were performed to assess glucose tolerance and insulin sensitivity. Outcome measures were IR (AUC(Insulin) and M values) on an OGTT and EHC, irisin levels, and metabolic markers. RESULTS: Circulating irisin was significantly higher in both overweight/obese (body mass index [BMI] ≥ 25 kg/m(2)) and PCOS women (P < .01). Circulating irisin levels correlated with BMI, WHR, FAT%, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), AUC(Insulin), homeostasis model assessment of insulin resistance (HOMA2-IR), M values, and free androgen index (FAI). During EHC, short-term hyperinsulinemia exhibited an inhibitory effect on irisin levels. After 6 months of metformin treatment, there was a significant decrease in circulating irisin in PCOS women following improved IR. CONCLUSIONS: These data suggest that irisin may be a useful marker of IR in PCOS women.
Integrity signals
Registry
Cites
Statistics
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?
Metformin might alleviate symptoms and treat PCOS by correcting abnormal levels of certain adipokines, such as resistin, visfatin, irisin, and chemerin.
“Metformin might alleviate the symptoms and treat PCOS by correcting the abnormal levels of certain adipokines, such as resistin, visfatin, irisin, and chemerin levels (18, 52–54).”
From Circulating Adipokine Levels in Nonobese Women with Polycystic Ovary Syndrome and in Nonobese Control Women: A Systematic Review and Meta-Analysis (2021) · cites this paper as [54]
Cites
(2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.10.004 · Cited by 9,050 · see citing works
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 · see citing works
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Dunaif, A. E. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.6.0318 · Cited by 2,761 · see citing works
Correct Homeostasis Model Assessment (HOMA) Evaluation Uses the Computer Program
Lévy, J., Matthews, D. R., & Hermans, M. P. (1998) · Diabetes Care · doi:10.2337/diacare.21.12.2191 · Cited by 1,997 · see citing works
A PGC1–α–dependent myokine that drives brown–fat–like development of white fat and thermogenesis
Ruth, M. (2012) · Yearbook of Endocrinology · doi:10.1016/j.yend.2012.04.012 · Cited by 1,687 · see citing works
Insulin Resistance and the Polycystic Ovary Syndrome: Mechanism and Implications for Pathogenesis
Dunaif, A. E. (1997) · Endocrine Reviews · doi:10.1210/er.18.6.774 · Cited by 1,167 · see citing works
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 · see citing works
Moreno-Navarrete, J. M., Ortega, F., Serrano, M., Guerra, E., Pardo, G., Tinahones, F., Ricart, W., & Fernández-Real, J. M. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2749 · Cited by 788 · see citing works
Lipoprotein Lipid Concentrations and Cardiovascular Risk in Women with Polycystic Ovary Syndrome
Wild, R. A., Painter, P. C., Coulson, P. B., CARRUTH, K. B., & Ranney, G. B. (1985) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-61-5-946 · Cited by 480 · see citing works
Lower circulating irisin is associated with type 2 diabetes mellitus
Liu, J., Wong, M. D. S., Toy, W. C., Tan, C., Liu, S., Ng, X. W., Subramaniam, T., Sum, C. F., & Lim, S. C. (2013) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2013.03.002 · Cited by 446 · see citing works
Stengel, A., Hofmann, T., Goebel-Stengel, M., Elbelt, U., Kobelt, P., & Klapp, B. (2013) · Peptides · doi:10.1016/j.peptides.2012.11.014 · Cited by 439 · see citing works
Serum irisin levels in new-onset type 2 diabetes
Choi, Y., Kim, M. K., Bae, K.-H., Seo, H.-A., Jeong, J.-Y., Lee, W.-K., Kim, J., Lee, I., & Park, K. (2013) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2013.01.007 · Cited by 422 · see citing works
Kurdiova, T., Balaz, M., Vician, M., Maderova, D., Vlcek, M., Valkovic, L., Srbecky, M., Imrich, R., Kyselovicova, O., Belan, V., et al. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.264655 · Cited by 401 · see citing works
Is irisin a human exercise gene?
Timmons, J. A., Baar, K., Davidsen, P. K., & Atherton, P. J. (2012) · Nature · doi:10.1038/nature11364 · Cited by 389 · see citing works
Kandaraki, E., Chatzigeorgiou, A., Livadas, S., Palioura, E., Economou, F., Koutsilieris, M., Palimeri, S., Panidis, D., & Diamanti‐Kandarakis, E. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2010-1658 · Cited by 387 · see citing works
Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis
Gilbert, C., Valois, M., & Koren, G. (2006) · Fertility and Sterility · doi:10.1016/j.fertnstert.2006.02.098 · Cited by 274 · see citing works
Diamanti‐Kandarakis, E., Katsikis, I., Piperi, C., Kandaraki, E., Piouka, A., Papavassiliou, A. G., & Panidis, D. (2008) · Clinical Endocrinology · doi:10.1111/j.1365-2265.2008.03247.x · Cited by 172 · see citing works
Cassina, M., Donà, M., Di Gianantonio, E., Litta, P., & Clementi, M. (2014) · Human Reproduction Update · doi:10.1093/humupd/dmu022 · Cited by 143 · see citing works
Metformin Treatment May Increase Omentin-1 Levels in Women With Polycystic Ovary Syndrome
Tan, B. K., Adya, R., Syed, F., Chen, J., Lehnert, H., & Randeva, H. S. (2010) · Diabetes · doi:10.2337/db10-0124 · Cited by 138 · see citing works
Diamanti‐Kandarakis, E. (2006) · Endocrine · doi:10.1385/endo:30:1:13 · Cited by 136 · see citing works
Spiegelman, B. M. (2013) · Diabetes · doi:10.2337/db12-1665 · Cited by 129 · see citing works
Accumulation of dietary glycotoxins in the reproductive system of normal female rats
Diamanti‐Kandarakis, E., Piperi, C., Korkolopoulou, P. A., Kandaraki, E., Levidou, G., Papalois, A. E., Patsouris, E., & Papavassiliou, A. G. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0246-6 · Cited by 104 · see citing works
Yang, M., Liu, R., Li, S., Luo, Y., Zhang, Y., Zhang, L., Liu, D., Wang, Y., Xiong, Z., Boden, G., et al. (2013) · Diabetes Care · doi:10.2337/dc12-0940 · Cited by 100 · see citing works
Self-citationDiet quality is associated with circulating C-reactive protein but not irisin levels in humans
Park, K., Zaichenko, L., Peter, P. R., Davis, C. R., Crowell, J. A., & Mantzoros, C. S. (2013) · Metabolism · doi:10.1016/j.metabol.2013.10.011 · Cited by 90 · see citing works
Serum levels of irisin in gestational diabetes mellitus during pregnancy and after delivery
Ebert, T., Stepan, H., Schrey-Petersen, S., Kralisch, S., Hindricks, J., Hopf, L., Platz, M., Lössner, U., Jeßnitzer, B., Drewlo, S., et al. (2013) · Cytokine · doi:10.1016/j.cyto.2013.11.009 · Cited by 85 · see citing works
Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome
Hutchison, S. K., Harrison, C. L., Stepto, N. K., Meyer, C., & Teede, H. J. (2008) · Diabetes Care · doi:10.2337/dc07-2265 · Cited by 51 · see citing works
Jia, Y., Yuan, L., Hu, W., Luo, Y., Suo, L., Yang, M., Chen, S., Wang, Y., Liu, H., Yang, G., et al. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12170 · Cited by 41 · see citing works
Self-citationZheng, J., Shan, P. F., & Gu, W. (2013) · PubMed · doi:10.3275/8932 · Cited by 31 · see citing works
Kandaraki, E., Chatzigeorgiou, A. E., Livadas, S., et al. (2010) · Endocrinology · doi:10.1210/endo.152.2.zee742b · Cited by 25 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
Polyzos, S. A., Anastasilakis, A. D., Efstathiadou, Z. A., Makras, P., Perakakis, N., Kountouras, J., & Mantzoros, C. S. (2018) · Endocrine · doi:10.1007/s12020-017-1476-1 · Cited by 262 · see citing works
Lin, K., Sun, X., Wang, X., Wang, H., & Chen, X. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.537809 · Cited by 81 · see citing works
Wang, Y., Xiang, T., Xia, X., Zhang, H., Geng, S., Yang, G., Qiu, S., He, Y., Liu, R., Li, L., et al. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1010714 · Cited by 5 · see citing works
Self-citation
- Authors
- Li, M., Yang, M., Zhou, X., Fang, X., Hu, W., Zhu, W., Wang, C., Liu, D., Li, S., Liu, H., Yang, G., & Li, L.
- Affiliations
- University of Mississippi Medical Center (US)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Chongqing Medical University (CN)
- Corresponding author
- Li, Ling
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-04
- Volume
- 100
- Issue
- 4
- Pages
- 1485-1493
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2158611249
- Cited by
- 115
- References
- 29
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 14 · 2023: 4 · 2022: 11 · 2021: 14 · 2020: 12 · 2019: 10 · 2018: 12 · 2017: 10 · 2016: 12 · 2015: 5
- FWCI
- 14.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (20105503110002, 81270913, 20125503110003)
- Chongqing Medical University
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- irisin, polycystic ovary syndrome, insulin resistance, metformin, insulin sensitivity, obesity, hyperinsulinemia, free androgen index, metabolic biomarkers, type 2 diabetes
- MeSH terms
- Adult, Cross-Sectional Studies, Female, Fibronectins, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Lipoproteins, LDL, Metformin, Obesity, Polycystic Ovary Syndrome, Up-Regulation, Overweight, Young Adult
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
