title: Physiology and role of irisin in glucose homeostasis.
abstract: 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.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Perakakis
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.
authors.forename: Georgios A
authors.initials: GA
authors.lastname: Triantafyllou
authors.affiliation: Department of Endocrinology, Hospital of Girona Doctor Josep Trueta, University of Girona, Emili Grahit Street, 17003 Girona, Spain.|Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición (CIBERobn), Avinguda de França, 17007 Girona, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Fernández-Real
authors.affiliation: College of Pharmacy, Chonnam National University, 77, Yongbong-ro, Buk-gu, Gwangju 61186, South Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Huh
authors.affiliation: Department of Family Medicine, Hallym University Sacred Heart Hospital, Hallym University, Gyeonggi-do 431070, South Korea.
authors.forename: Kyung Hee
authors.initials: KH
authors.lastname: Park
authors.affiliation: Division of Endocrinology and Diabetology, Department of Internal Medicine II, University Hospital of Freiburg, Faculty of Medicine, University of Freiburg, 55 Hugstetter Street, 79106 Freiburg, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Seufert
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA.|Section of Endocrinology, Boston VA Healthcare System, Harvard Medical School, 150 South Huntington Avenue, Boston, Massachusetts 02130, USA.
authors.forename: Christos S
authors.initials: CS
authors.lastname: Mantzoros
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2; D015444:Exercise; D005353:Fibronectins / Q000032:analysis / Q000097:blood / Q000502:physiology*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008659:Metabolic Diseases; D024821:Metabolic Syndrome; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity; D010179:Pancreas / Q000378:metabolism
chemical_list: C577593:FNDC5 protein, human; D005353:Fibronectins; D005947:Glucose