Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle

•Exercise enhanced M2 macrophage accumulation and insulin sensitivity in muscle.•Macrophage depletion cancelled the enhanced insulin sensitivity by exercise.•Macrophage depletion also inhibited the M2 macrophage accumulation in muscle.•Insulin signaling and GLUT4 content were not affected by macroph...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2013-11, Vol.441 (1), p.36-41
Main Authors: Ikeda, Shin-ichi, Tamura, Yoshifumi, Kakehi, Saori, Takeno, Kageumi, Kawaguchi, Minako, Watanabe, Takahiro, Sato, Fumihiko, Ogihara, Takeshi, Kanazawa, Akio, Fujitani, Yoshio, Kawamori, Ryuzo, Watada, Hirotaka
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - metabolism
Antigens, Differentiation, Myelomonocytic - metabolism
Cell Polarity - drug effects
Clodronic Acid - administration & dosage
Clodronic Acid - pharmacology
Deoxyglucose - metabolism
Exercise
Glucose Transporter Type 4 - metabolism
GTPase-Activating Proteins - metabolism
Insulin - pharmacology
Insulin sensitivity
Liposomes
M2 macrophages
Macrophages - cytology
Macrophages - drug effects
Macrophages - enzymology
Male
Mice
Mice, Inbred C57BL
Muscle, Skeletal - cytology
Phosphorylation - drug effects
Physical Conditioning, Animal
Proto-Oncogene Proteins c-akt - metabolism
Receptors, Cell Surface - metabolism
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Summary:•Exercise enhanced M2 macrophage accumulation and insulin sensitivity in muscle.•Macrophage depletion cancelled the enhanced insulin sensitivity by exercise.•Macrophage depletion also inhibited the M2 macrophage accumulation in muscle.•Insulin signaling and GLUT4 content were not affected by macrophage depletion. 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 (20m/min, 90min). 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2013.10.005