title: Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle.
abstract: Exercise enhances insulin sensitivity in skeletal muscle, but the underlying mechanism remains obscure. Recent data suggest that alternatively activated M2 macrophages enhance insulin sensitivity in insulin target organs such as adipose tissue and liver. Therefore, the aim of this study was to determine the role of anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2-deoxy glucose uptake was found to be increased in plantaris muscle. This change was associated with increased number of CD163-expressing macrophages (i.e. M2-polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by pretreatment of mice with clodronate-containing liposome abrogated both CD163-positive macrophage accumulation in skeletal muscle as well as the enhancement of insulin sensitivity after exercise, without affecting insulin-induced phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These results suggest that accumulation of M2-polarized macrophages is involved in exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle, independently of the phosphorylation of Akt and AS160 and expression of GLUT4.
authors.affiliation: Department of Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan; Sportology Center, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Saori
authors.initials: S
authors.lastname: Kakehi
authors.forename: Kageumi
authors.initials: K
authors.lastname: Takeno
authors.forename: Minako
authors.initials: M
authors.lastname: Kawaguchi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ogihara
authors.forename: Akio
authors.initials: A
authors.lastname: Kanazawa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D016764:Cell Polarity / Q000187:drug effects*; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008081:Liposomes; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology*; D010766:Phosphorylation / Q000187:drug effects; D010805:Physical Conditioning, Animal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D008081:Liposomes; D011956:Receptors, Cell Surface; C495693:Slc2a4 protein, mouse; C505647:Tbc1d4 protein, mouse; D004002:Clodronic Acid; D003847:Deoxyglucose; D051057:Proto-Oncogene Proteins c-akt
keywords: Exercise; Insulin sensitivity; M2 macrophages