Regulation of Glucose Transport by ROCK1 Differs from That of ROCK2 and Is Controlled by Actin Polymerization
A role of Rho-associated coiled-coil-containing protein kinase (ROCK)1 in regulating whole-body glucose homeostasis has been reported. However, cell-autonomous effects of ROCK1 on insulin-dependent glucose transport in adipocytes and muscle cells have not been elucidated. To determine the specific r...
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| Veröffentlicht in: | Endocrinology (Philadelphia) 2012-04, Vol.153 (4), p.1649-1662 |
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| creator | Chun, Kwang-Hoon Araki, Kazushi Jee, Yuna Lee, Dae-Ho Oh, Byung-Chul Huang, Hu Park, Kyong Soo Lee, Sam W Zabolotny, Janice M Kim, Young-Bum |
| description | A role of Rho-associated coiled-coil-containing protein kinase (ROCK)1 in regulating whole-body glucose homeostasis has been reported. However, cell-autonomous effects of ROCK1 on insulin-dependent glucose transport in adipocytes and muscle cells have not been elucidated. To determine the specific role of ROCK1 in glucose transport directly, ROCK1 expression in 3T3-L1 adipocytes and L6 myoblasts was biologically modulated. Here, we show that small interfering RNA-mediated ROCK1 depletion decreased insulin-induced glucose transport in adipocytes and myoblasts, whereas adenovirus-mediated ROCK1 expression increased this in a dose-dependent manner, indicating that ROCK1 is permissive for glucose transport. Inhibition of ROCK1 also impaired glucose transporter 4 translocation in 3T3-L1 adipocytes. Importantly, the ED50 of insulin for adipocyte glucose transport was reduced when ROCK1 was expressed, leading to hypersensitivity to insulin. These effects are dependent on actin cytoskeleton remodeling, because inhibitors of actin polymerization significantly decreased ROCK1's effect to promote insulin-stimulated glucose transport. Unlike ROCK2, ROCK1 binding to insulin receptor substrate (IRS)-1 was not detected by immunoprecipitation, although cell fractionation demonstrated both ROCK isoforms localize with IRS-1 in low-density microsomes. Moreover, insulin's ability to increase IRS-1 tyrosine 612 and serine 632/635 phosphorylation was attenuated by ROCK1 suppression. Replacing IRS-1 serine 632/635 with alanine reduced insulin-stimulated phosphatidylinositol 3-kinase activation and glucose transport in 3T3-L1 adipocytes, indicating that phosphorylation of these serine residues of IRS-1, which are substrates of the ROCK2 isoform in vitro, are crucial for maximal stimulation of glucose transport by insulin. Our studies identify ROCK1 as an important positive regulator of insulin action on glucose transport in adipocytes and muscle cells. |
| doi_str_mv | 10.1210/en.2011-1036 |
| format | Article |
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However, cell-autonomous effects of ROCK1 on insulin-dependent glucose transport in adipocytes and muscle cells have not been elucidated. To determine the specific role of ROCK1 in glucose transport directly, ROCK1 expression in 3T3-L1 adipocytes and L6 myoblasts was biologically modulated. Here, we show that small interfering RNA-mediated ROCK1 depletion decreased insulin-induced glucose transport in adipocytes and myoblasts, whereas adenovirus-mediated ROCK1 expression increased this in a dose-dependent manner, indicating that ROCK1 is permissive for glucose transport. Inhibition of ROCK1 also impaired glucose transporter 4 translocation in 3T3-L1 adipocytes. Importantly, the ED50 of insulin for adipocyte glucose transport was reduced when ROCK1 was expressed, leading to hypersensitivity to insulin. These effects are dependent on actin cytoskeleton remodeling, because inhibitors of actin polymerization significantly decreased ROCK1's effect to promote insulin-stimulated glucose transport. Unlike ROCK2, ROCK1 binding to insulin receptor substrate (IRS)-1 was not detected by immunoprecipitation, although cell fractionation demonstrated both ROCK isoforms localize with IRS-1 in low-density microsomes. Moreover, insulin's ability to increase IRS-1 tyrosine 612 and serine 632/635 phosphorylation was attenuated by ROCK1 suppression. Replacing IRS-1 serine 632/635 with alanine reduced insulin-stimulated phosphatidylinositol 3-kinase activation and glucose transport in 3T3-L1 adipocytes, indicating that phosphorylation of these serine residues of IRS-1, which are substrates of the ROCK2 isoform in vitro, are crucial for maximal stimulation of glucose transport by insulin. Our studies identify ROCK1 as an important positive regulator of insulin action on glucose transport in adipocytes and muscle cells.</description><identifier>ISSN: 0013-7227</identifier><identifier>EISSN: 1945-7170</identifier><identifier>DOI: 10.1210/en.2011-1036</identifier><identifier>PMID: 22355071</identifier><identifier>CODEN: ENDOAO</identifier><language>eng</language><publisher>Chevy Chase, MD: Endocrine Society</publisher><subject>1-Phosphatidylinositol 3-kinase ; 3T3-L1 Cells ; Actin ; Actins - metabolism ; Adipocytes ; Adipocytes - cytology ; Adipocytes - drug effects ; Adipocytes - metabolism ; Alanine ; Animals ; Biological and medical sciences ; Biological Transport - physiology ; Cells, Cultured ; Cytoskeleton ; Diabetes-Insulin-Glucagon-Gastrointestinal ; Fractionation ; Fundamental and applied biological sciences. Psychology ; Glucose ; Glucose - metabolism ; Glucose transport ; Glucose transporter ; Glucose Transporter Type 4 - metabolism ; Homeostasis ; Hypersensitivity ; Immunoprecipitation ; In Vitro Techniques ; Insulin ; Insulin - pharmacology ; Insulin receptor substrate 1 ; Insulin Receptor Substrate Proteins - metabolism ; Isoforms ; Kinases ; Mice ; Microsomes ; Models, Animal ; Muscles ; Myoblasts ; Myoblasts, Skeletal - cytology ; Myoblasts, Skeletal - drug effects ; Myoblasts, Skeletal - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Polymerization ; rho-Associated Kinases - metabolism ; RNA transport ; Rocks ; siRNA ; Substrate inhibition ; Translocation ; Tyrosine ; Vertebrates: endocrinology</subject><ispartof>Endocrinology (Philadelphia), 2012-04, Vol.153 (4), p.1649-1662</ispartof><rights>Copyright © 2012 by The Endocrine Society</rights><rights>Copyright © 2012 by The Endocrine Society 2012</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-94c5e7742469ac6018806c72e5cf7e5471eecdea63a599ee7f4e6c8ff6dc8f8c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25773192$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22355071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chun, Kwang-Hoon</creatorcontrib><creatorcontrib>Araki, Kazushi</creatorcontrib><creatorcontrib>Jee, Yuna</creatorcontrib><creatorcontrib>Lee, Dae-Ho</creatorcontrib><creatorcontrib>Oh, Byung-Chul</creatorcontrib><creatorcontrib>Huang, Hu</creatorcontrib><creatorcontrib>Park, Kyong Soo</creatorcontrib><creatorcontrib>Lee, Sam W</creatorcontrib><creatorcontrib>Zabolotny, Janice M</creatorcontrib><creatorcontrib>Kim, Young-Bum</creatorcontrib><title>Regulation of Glucose Transport by ROCK1 Differs from That of ROCK2 and Is Controlled by Actin Polymerization</title><title>Endocrinology (Philadelphia)</title><addtitle>Endocrinology</addtitle><description>A role of Rho-associated coiled-coil-containing protein kinase (ROCK)1 in regulating whole-body glucose homeostasis has been reported. However, cell-autonomous effects of ROCK1 on insulin-dependent glucose transport in adipocytes and muscle cells have not been elucidated. To determine the specific role of ROCK1 in glucose transport directly, ROCK1 expression in 3T3-L1 adipocytes and L6 myoblasts was biologically modulated. Here, we show that small interfering RNA-mediated ROCK1 depletion decreased insulin-induced glucose transport in adipocytes and myoblasts, whereas adenovirus-mediated ROCK1 expression increased this in a dose-dependent manner, indicating that ROCK1 is permissive for glucose transport. Inhibition of ROCK1 also impaired glucose transporter 4 translocation in 3T3-L1 adipocytes. Importantly, the ED50 of insulin for adipocyte glucose transport was reduced when ROCK1 was expressed, leading to hypersensitivity to insulin. These effects are dependent on actin cytoskeleton remodeling, because inhibitors of actin polymerization significantly decreased ROCK1's effect to promote insulin-stimulated glucose transport. Unlike ROCK2, ROCK1 binding to insulin receptor substrate (IRS)-1 was not detected by immunoprecipitation, although cell fractionation demonstrated both ROCK isoforms localize with IRS-1 in low-density microsomes. Moreover, insulin's ability to increase IRS-1 tyrosine 612 and serine 632/635 phosphorylation was attenuated by ROCK1 suppression. Replacing IRS-1 serine 632/635 with alanine reduced insulin-stimulated phosphatidylinositol 3-kinase activation and glucose transport in 3T3-L1 adipocytes, indicating that phosphorylation of these serine residues of IRS-1, which are substrates of the ROCK2 isoform in vitro, are crucial for maximal stimulation of glucose transport by insulin. Our studies identify ROCK1 as an important positive regulator of insulin action on glucose transport in adipocytes and muscle cells.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>3T3-L1 Cells</subject><subject>Actin</subject><subject>Actins - metabolism</subject><subject>Adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Alanine</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biological Transport - physiology</subject><subject>Cells, Cultured</subject><subject>Cytoskeleton</subject><subject>Diabetes-Insulin-Glucagon-Gastrointestinal</subject><subject>Fractionation</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucose transport</subject><subject>Glucose transporter</subject><subject>Glucose Transporter Type 4 - metabolism</subject><subject>Homeostasis</subject><subject>Hypersensitivity</subject><subject>Immunoprecipitation</subject><subject>In Vitro Techniques</subject><subject>Insulin</subject><subject>Insulin - pharmacology</subject><subject>Insulin receptor substrate 1</subject><subject>Insulin Receptor Substrate Proteins - metabolism</subject><subject>Isoforms</subject><subject>Kinases</subject><subject>Mice</subject><subject>Microsomes</subject><subject>Models, Animal</subject><subject>Muscles</subject><subject>Myoblasts</subject><subject>Myoblasts, Skeletal - cytology</subject><subject>Myoblasts, Skeletal - drug effects</subject><subject>Myoblasts, Skeletal - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Polymerization</subject><subject>rho-Associated Kinases - metabolism</subject><subject>RNA transport</subject><subject>Rocks</subject><subject>siRNA</subject><subject>Substrate inhibition</subject><subject>Translocation</subject><subject>Tyrosine</subject><subject>Vertebrates: endocrinology</subject><issn>0013-7227</issn><issn>1945-7170</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kd1rFDEUxYModq2--SwBkb44NV8zmbwIZau1WKiU9TmkmZs2JZNskxlh_eudcdeuir4khPvLOedyEHpJyTFllLyDeMwIpRUlvHmEFlSJupJUksdoQQjllWRMHqBnpdxNTyEEf4oOGON1TSRdoP4KbsZgBp8iTg6fhdGmAniVTSzrlAd8vcFXl8vPFJ965yAX7HLq8erWDDM_jxg2scPnBS9THHIKAbr514kdfMRfUtj0kP33nxbP0RNnQoEXu_sQff34YbX8VF1cnp0vTy4qW1M5VErYGqQUTDTK2IbQtiWNlQxq6yTUQlIA24FpuKmVApBOQGNb55puOlvLD9H7re56vO6hszAFM0Gvs-9N3uhkvP5zEv2tvknfNOeMsIZOAkc7gZzuRyiD7n2xEIKJkMailWgV5YKoiXz9F3mXxhyn7TSnnDRUETXrvd1SNqdSMriHLJTouUYNUc816rnGCX_1e_4H-FdvE_BmB5hiTXBTXdaXPVdLyali-z3SuP6fZbWz5FsSYpds9hHWGUrZb_PPoD8ADxbCNQ</recordid><startdate>20120401</startdate><enddate>20120401</enddate><creator>Chun, Kwang-Hoon</creator><creator>Araki, Kazushi</creator><creator>Jee, Yuna</creator><creator>Lee, Dae-Ho</creator><creator>Oh, Byung-Chul</creator><creator>Huang, Hu</creator><creator>Park, Kyong Soo</creator><creator>Lee, Sam W</creator><creator>Zabolotny, Janice M</creator><creator>Kim, Young-Bum</creator><general>Endocrine Society</general><general>Oxford University Press</general><scope>IQODW</scope><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>7QG</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120401</creationdate><title>Regulation of Glucose Transport by ROCK1 Differs from That of ROCK2 and Is Controlled by Actin Polymerization</title><author>Chun, Kwang-Hoon ; Araki, Kazushi ; Jee, Yuna ; Lee, Dae-Ho ; Oh, Byung-Chul ; Huang, Hu ; Park, Kyong Soo ; Lee, Sam W ; Zabolotny, Janice M ; Kim, Young-Bum</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-94c5e7742469ac6018806c72e5cf7e5471eecdea63a599ee7f4e6c8ff6dc8f8c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>3T3-L1 Cells</topic><topic>Actin</topic><topic>Actins - metabolism</topic><topic>Adipocytes</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - drug effects</topic><topic>Adipocytes - metabolism</topic><topic>Alanine</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biological Transport - physiology</topic><topic>Cells, Cultured</topic><topic>Cytoskeleton</topic><topic>Diabetes-Insulin-Glucagon-Gastrointestinal</topic><topic>Fractionation</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Glucose transport</topic><topic>Glucose transporter</topic><topic>Glucose Transporter Type 4 - metabolism</topic><topic>Homeostasis</topic><topic>Hypersensitivity</topic><topic>Immunoprecipitation</topic><topic>In Vitro Techniques</topic><topic>Insulin</topic><topic>Insulin - pharmacology</topic><topic>Insulin receptor substrate 1</topic><topic>Insulin Receptor Substrate Proteins - metabolism</topic><topic>Isoforms</topic><topic>Kinases</topic><topic>Mice</topic><topic>Microsomes</topic><topic>Models, Animal</topic><topic>Muscles</topic><topic>Myoblasts</topic><topic>Myoblasts, Skeletal - cytology</topic><topic>Myoblasts, Skeletal - drug effects</topic><topic>Myoblasts, Skeletal - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Polymerization</topic><topic>rho-Associated Kinases - metabolism</topic><topic>RNA transport</topic><topic>Rocks</topic><topic>siRNA</topic><topic>Substrate inhibition</topic><topic>Translocation</topic><topic>Tyrosine</topic><topic>Vertebrates: endocrinology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chun, Kwang-Hoon</creatorcontrib><creatorcontrib>Araki, Kazushi</creatorcontrib><creatorcontrib>Jee, Yuna</creatorcontrib><creatorcontrib>Lee, Dae-Ho</creatorcontrib><creatorcontrib>Oh, Byung-Chul</creatorcontrib><creatorcontrib>Huang, Hu</creatorcontrib><creatorcontrib>Park, Kyong Soo</creatorcontrib><creatorcontrib>Lee, Sam W</creatorcontrib><creatorcontrib>Zabolotny, Janice M</creatorcontrib><creatorcontrib>Kim, Young-Bum</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Endocrinology (Philadelphia)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chun, Kwang-Hoon</au><au>Araki, Kazushi</au><au>Jee, Yuna</au><au>Lee, Dae-Ho</au><au>Oh, Byung-Chul</au><au>Huang, Hu</au><au>Park, Kyong Soo</au><au>Lee, Sam W</au><au>Zabolotny, Janice M</au><au>Kim, Young-Bum</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of Glucose Transport by ROCK1 Differs from That of ROCK2 and Is Controlled by Actin Polymerization</atitle><jtitle>Endocrinology (Philadelphia)</jtitle><addtitle>Endocrinology</addtitle><date>2012-04-01</date><risdate>2012</risdate><volume>153</volume><issue>4</issue><spage>1649</spage><epage>1662</epage><pages>1649-1662</pages><issn>0013-7227</issn><eissn>1945-7170</eissn><coden>ENDOAO</coden><abstract>A role of Rho-associated coiled-coil-containing protein kinase (ROCK)1 in regulating whole-body glucose homeostasis has been reported. However, cell-autonomous effects of ROCK1 on insulin-dependent glucose transport in adipocytes and muscle cells have not been elucidated. To determine the specific role of ROCK1 in glucose transport directly, ROCK1 expression in 3T3-L1 adipocytes and L6 myoblasts was biologically modulated. Here, we show that small interfering RNA-mediated ROCK1 depletion decreased insulin-induced glucose transport in adipocytes and myoblasts, whereas adenovirus-mediated ROCK1 expression increased this in a dose-dependent manner, indicating that ROCK1 is permissive for glucose transport. Inhibition of ROCK1 also impaired glucose transporter 4 translocation in 3T3-L1 adipocytes. Importantly, the ED50 of insulin for adipocyte glucose transport was reduced when ROCK1 was expressed, leading to hypersensitivity to insulin. These effects are dependent on actin cytoskeleton remodeling, because inhibitors of actin polymerization significantly decreased ROCK1's effect to promote insulin-stimulated glucose transport. Unlike ROCK2, ROCK1 binding to insulin receptor substrate (IRS)-1 was not detected by immunoprecipitation, although cell fractionation demonstrated both ROCK isoforms localize with IRS-1 in low-density microsomes. Moreover, insulin's ability to increase IRS-1 tyrosine 612 and serine 632/635 phosphorylation was attenuated by ROCK1 suppression. Replacing IRS-1 serine 632/635 with alanine reduced insulin-stimulated phosphatidylinositol 3-kinase activation and glucose transport in 3T3-L1 adipocytes, indicating that phosphorylation of these serine residues of IRS-1, which are substrates of the ROCK2 isoform in vitro, are crucial for maximal stimulation of glucose transport by insulin. Our studies identify ROCK1 as an important positive regulator of insulin action on glucose transport in adipocytes and muscle cells.</abstract><cop>Chevy Chase, MD</cop><pub>Endocrine Society</pub><pmid>22355071</pmid><doi>10.1210/en.2011-1036</doi><tpages>14</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Journals@Ovid Complete; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | 1-Phosphatidylinositol 3-kinase 3T3-L1 Cells Actin Actins - metabolism Adipocytes Adipocytes - cytology Adipocytes - drug effects Adipocytes - metabolism Alanine Animals Biological and medical sciences Biological Transport - physiology Cells, Cultured Cytoskeleton Diabetes-Insulin-Glucagon-Gastrointestinal Fractionation Fundamental and applied biological sciences. Psychology Glucose Glucose - metabolism Glucose transport Glucose transporter Glucose Transporter Type 4 - metabolism Homeostasis Hypersensitivity Immunoprecipitation In Vitro Techniques Insulin Insulin - pharmacology Insulin receptor substrate 1 Insulin Receptor Substrate Proteins - metabolism Isoforms Kinases Mice Microsomes Models, Animal Muscles Myoblasts Myoblasts, Skeletal - cytology Myoblasts, Skeletal - drug effects Myoblasts, Skeletal - metabolism Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Polymerization rho-Associated Kinases - metabolism RNA transport Rocks siRNA Substrate inhibition Translocation Tyrosine Vertebrates: endocrinology |
| title | Regulation of Glucose Transport by ROCK1 Differs from That of ROCK2 and Is Controlled by Actin Polymerization |
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