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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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| Published in: | Biochemical and biophysical research communications 2013-11, Vol.441 (1), p.36-41 |
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| container_title | Biochemical and biophysical research communications |
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| creator | 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 |
| description | •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. |
| doi_str_mv | 10.1016/j.bbrc.2013.10.005 |
| format | article |
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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.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2013.10.005</identifier><identifier>PMID: 24120496</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>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</subject><ispartof>Biochemical and biophysical research communications, 2013-11, Vol.441 (1), p.36-41</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-b8586cec90a50c9798fcae79afbfe1a05fcba9271c55d17b833672c334e70aec3</citedby><cites>FETCH-LOGICAL-c356t-b8586cec90a50c9798fcae79afbfe1a05fcba9271c55d17b833672c334e70aec3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,786,790,27957,27958</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24120496$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ikeda, Shin-ichi</creatorcontrib><creatorcontrib>Tamura, Yoshifumi</creatorcontrib><creatorcontrib>Kakehi, Saori</creatorcontrib><creatorcontrib>Takeno, Kageumi</creatorcontrib><creatorcontrib>Kawaguchi, Minako</creatorcontrib><creatorcontrib>Watanabe, Takahiro</creatorcontrib><creatorcontrib>Sato, Fumihiko</creatorcontrib><creatorcontrib>Ogihara, Takeshi</creatorcontrib><creatorcontrib>Kanazawa, Akio</creatorcontrib><creatorcontrib>Fujitani, Yoshio</creatorcontrib><creatorcontrib>Kawamori, Ryuzo</creatorcontrib><creatorcontrib>Watada, Hirotaka</creatorcontrib><title>Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>•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.</description><subject>Animals</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - metabolism</subject><subject>Cell Polarity - drug effects</subject><subject>Clodronic Acid - administration & dosage</subject><subject>Clodronic Acid - pharmacology</subject><subject>Deoxyglucose - metabolism</subject><subject>Exercise</subject><subject>Glucose Transporter Type 4 - metabolism</subject><subject>GTPase-Activating Proteins - metabolism</subject><subject>Insulin - pharmacology</subject><subject>Insulin sensitivity</subject><subject>Liposomes</subject><subject>M2 macrophages</subject><subject>Macrophages - cytology</subject><subject>Macrophages - drug effects</subject><subject>Macrophages - enzymology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Muscle, Skeletal - cytology</subject><subject>Phosphorylation - drug effects</subject><subject>Physical Conditioning, Animal</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Receptors, Cell Surface - metabolism</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kU9v1DAQxS0EotvCF-CAfOSSZez8l7igqi2VirhQiZvlTCasFydZPE5p-QT92DjawpHTSKPfe5p5T4g3CrYKVPV-v-26gFsNKk-LLUD5TGwUtJBpBcVzsQGAKtOt-nYiTpn3AEoVVftSnOhCaSjaaiMeL-4poGPK3NQvSL2kaWcnpJGmKOdBuokX7ybJNLGL7s7FB-lYWuYZnY1J8MvFnbSIy7h4G908rbLPOjvM3gb3OxGjxTAfdvY7cfKT47wwSf5BnqL1clwYPb0SLwbrmV4_zTNxe3nx9fxTdvPl6vr8402GeVnFrGvKpkLCFmwJ2NZtM6ClurVDN5CyUA7Y2VbXCsuyV3XX5HlVa8zzgmqwhPmZeHf0PYT550IczegYyXs7UbrLqKIE1eiqaRKqj2i6njnQYA7BjTY8GAVmbcDszdqAWRtYd6mBJHr75L90I_X_JH8jT8CHI0DpyztHwTA6Son3LhBG08_uf_5_APSMmyk</recordid><startdate>20131108</startdate><enddate>20131108</enddate><creator>Ikeda, Shin-ichi</creator><creator>Tamura, Yoshifumi</creator><creator>Kakehi, Saori</creator><creator>Takeno, Kageumi</creator><creator>Kawaguchi, Minako</creator><creator>Watanabe, Takahiro</creator><creator>Sato, Fumihiko</creator><creator>Ogihara, Takeshi</creator><creator>Kanazawa, Akio</creator><creator>Fujitani, Yoshio</creator><creator>Kawamori, Ryuzo</creator><creator>Watada, Hirotaka</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20131108</creationdate><title>Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-b8586cec90a50c9798fcae79afbfe1a05fcba9271c55d17b833672c334e70aec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Antigens, CD - metabolism</topic><topic>Antigens, Differentiation, Myelomonocytic - metabolism</topic><topic>Cell Polarity - drug effects</topic><topic>Clodronic Acid - administration & dosage</topic><topic>Clodronic Acid - pharmacology</topic><topic>Deoxyglucose - metabolism</topic><topic>Exercise</topic><topic>Glucose Transporter Type 4 - metabolism</topic><topic>GTPase-Activating Proteins - metabolism</topic><topic>Insulin - pharmacology</topic><topic>Insulin sensitivity</topic><topic>Liposomes</topic><topic>M2 macrophages</topic><topic>Macrophages - cytology</topic><topic>Macrophages - drug effects</topic><topic>Macrophages - enzymology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Muscle, Skeletal - cytology</topic><topic>Phosphorylation - drug effects</topic><topic>Physical Conditioning, Animal</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Receptors, Cell Surface - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ikeda, Shin-ichi</creatorcontrib><creatorcontrib>Tamura, Yoshifumi</creatorcontrib><creatorcontrib>Kakehi, Saori</creatorcontrib><creatorcontrib>Takeno, Kageumi</creatorcontrib><creatorcontrib>Kawaguchi, Minako</creatorcontrib><creatorcontrib>Watanabe, Takahiro</creatorcontrib><creatorcontrib>Sato, Fumihiko</creatorcontrib><creatorcontrib>Ogihara, Takeshi</creatorcontrib><creatorcontrib>Kanazawa, Akio</creatorcontrib><creatorcontrib>Fujitani, Yoshio</creatorcontrib><creatorcontrib>Kawamori, Ryuzo</creatorcontrib><creatorcontrib>Watada, Hirotaka</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ikeda, Shin-ichi</au><au>Tamura, Yoshifumi</au><au>Kakehi, Saori</au><au>Takeno, Kageumi</au><au>Kawaguchi, Minako</au><au>Watanabe, Takahiro</au><au>Sato, Fumihiko</au><au>Ogihara, Takeshi</au><au>Kanazawa, Akio</au><au>Fujitani, Yoshio</au><au>Kawamori, Ryuzo</au><au>Watada, Hirotaka</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2013-11-08</date><risdate>2013</risdate><volume>441</volume><issue>1</issue><spage>36</spage><epage>41</epage><pages>36-41</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-2</notes><notes>content type line 23</notes><abstract>•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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24120496</pmid><doi>10.1016/j.bbrc.2013.10.005</doi><tpages>6</tpages></addata></record> |
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| 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 |
| title | Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle |
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