Physiology and role of irisin in glucose homeostasis
Open accessAbstract
Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned. In this Review, we present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome.
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Although still controversial, it is generally agreed that irisin levels increase transiently following acute bouts of aerobic and resistance exercise, which could contribute to loss of fat mass.
“Although still controversial [56], it is generally agreed that irisin levels increase transiently following acute bouts of aerobic and resistance exercise [40], which could contribute to loss of fat mass.”
Some exercise-induced factors have direct insulin-sensitizing effects in target tissues, independently of their effect on inflammation, such as irisin, IL-6, IL-15, METRNL, BAIBA, and FGF21.
“Importantly, some exercise-induced factors have also been shown to have direct insulin-sensitizing effects in target tissues, independently of their effect on inflammation, such as irisin [56], IL-6 [122], IL-15 [84], METRNL [274], BAIBA [112], and FGF21 [154] (10).”
Irisin can increase muscle oxidative metabolism and substrate uptake, and reduce hepatic glucose output.
“Irisin can also increase muscle oxidative metabolism and substrate (glucose and fatty acid) uptake, and reduce hepatic glucose output 117.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [117]
Irisin treatment can positively affect glucose and lipid metabolism in mice.
“Finally, despite evidence that irisin treatment can positively affect glucose and lipid metabolism in mice, no real consensus exists as of yet concerning the link between irisin and the metabolic syndrome in humans, and no irisin analog has been used for studies in humans 117.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [117]
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Circulating irisin is lower in gestational diabetes mellitus
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The effect of Irisin on antioxidant system in liver
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Research works printed but not linked: 3
- [5]NCBI Fibronectin type III domain-containing protein 5 precursor [Rattus norvegicus] NCBI https://www.ncbi.nlm.nih.gov/protein/NP_001257910.1 2016
- [6]NCBI Fibronectin type III domain-containing protein 5 preproprotein [Mus musculus] NCBI https://www.ncbi.nlm.nih.gov/protein/NP_081678.1 2016
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Irisin Mediates Effects on Bone and Fat via αV Integrin Receptors
Kim, H., Wrann, C. D., Jedrychowski, M., Vidoni, S., Kitase, Y., Nagano, K., Zhou, C., Chou, J., Parkman, V.-J. A., Novick, S. J., et al. (2018) · Cell · doi:10.1016/j.cell.2018.10.025 · Cited by 638 · see citing works
“—Since its discovery in 2012, irisin has been reported to have various functions in many organs (Perakakis et al., 2017; Polyzos et al., 2018).”
Gonzalez-Gil, A. M., & Elizondo-Montemayor, L. (2020) · Nutrients · doi:10.3390/nu12061899 · Cited by 278 · see citing works
“Irisin Ob: ↑ [39]+; T2DM: ↓ [39]+ AE: ↑ (aerobic or resistance) [40]+ CE: ↓? (aerobic or resistance) [41]+ ↑ (via PGC-1α): cold-induced shivering [42], ↑AMP:ATP ratio (via AMPK-PGC-1α pathway), FGF21* [43], and METRNL (via ↑PGC-1α4)* [44] ↓: proinflammatory cytokines [45] (possibly via NF-kB-mediated inhibition of PGC…”
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Self-citationProgress and Challenges in the Biology of FNDC5 and Irisin
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The role of exercise-induced myokines in regulating metabolism
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Inter‐organ communication: a gatekeeper for metabolic health
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Myokines mediate the cross talk between skeletal muscle and other organs
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Exercise induces white adipose tissue browning across the weight spectrum in humans
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Irisin, an exercise-induced bioactive peptide beneficial for health promotion during aging process
Zhang, H., Wu, X., Liang, J., Kirberger, M., & Chen, N. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101680 · Cited by 88 · see citing works
Sarcopenic obesity: Myokines as potential diagnostic biomarkers and therapeutic targets?
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Targeting obesity and diabetes to treat heart failure with preserved ejection fraction
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Myokine/Adipokine response to “Aerobic” exercise: Is it just a matter of exercise load?
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“3 ng/mL (~358 pmol/L) in individuals undergoing aerobic interval training, currently available ELISA assays for quantifying circulating irisin levels still lack of quality and accuracy, and the measured values are very dissimilar between the different assays [18,20].”
BackgroundMyokines: Metabolic regulation in obesity and type 2 diabetes
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Irisin increases the expression of anorexigenic and neurotrophic genes in mouse brain
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- Authors
- Perakakis, N., Triantafyllou, G. A., Fernández-Real, J. M., Huh, J. Y., Park, K. H., Seufert, J., & Mantzoros, C. S.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Chonnam National University (KR)
- Hallym University Sacred Heart Hospital (KR)
- University of Freiburg (DE)
- Corresponding author
- Perakakis, Nikolaos
- Mantzoros, Christos S.
- ORCID
- Venue
- Nature Reviews Endocrinology
- Published
- 2017-02-17
- Volume
- 13
- Issue
- 6
- Pages
- 324-337
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- PMC
- PMC5878942
- OpenAlex
- W2587815451
- Cited by
- 621
- References
- 138
- Citations by year
- 2026: 38 · 2025: 58 · 2024: 81 · 2023: 66 · 2022: 96 · 2021: 92 · 2020: 76 · 2019: 50 · 2018: 44 · 2017: 20
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K24DK081913)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- irisin, myokines, glucose homeostasis, insulin resistance, type 2 diabetes, metabolic syndrome, obesity, white adipose tissue browning, energy expenditure
- MeSH terms
- Adipose Tissue, Animals, Diabetes Mellitus, Type 2, Fibronectins, Glucose, Homeostasis, Humans, Insulin Resistance, Liver, Metabolic Diseases, Obesity, Pancreas, Exercise, Muscle, Skeletal, Metabolic Syndrome
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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 ›
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