In vivo Effect of Insulin to Decrease Matrix Metalloproteinase-2 and -9 Activity after Arterial Injury
In vitro, insulin has both growth-promoting and vasculoprotective effects. In vivo, the effect of insulin is mainly protective. Insulin treatment (3 U/day) decreases smooth muscle cell (SMC) migration and neointimal growth after carotid angioplasty in normal rats maintained at normoglycemia by oral...
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| Veröffentlicht in: | Journal of vascular research 2013-01, Vol.50 (4), p.279-288 |
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| creator | Guo, June Dhaliwall, Jiwanjeet K. Chan, Kalam K. Ghanim, Husam Al Koudsi, Nael Lam, Loretta Madadi, Golnaz Dandona, Paresh Giacca, Adria Bendeck, Michelle P. |
| description | In vitro, insulin has both growth-promoting and vasculoprotective effects. In vivo, the effect of insulin is mainly protective. Insulin treatment (3 U/day) decreases smooth muscle cell (SMC) migration and neointimal growth after carotid angioplasty in normal rats maintained at normoglycemia by oral glucose. SMC migration requires limited proteolysis of the extracellular matrix, which is mediated by matrix metalloproteinases (MMPs). In this study, we investigated the effects of normoglycemic hyperinsulinemia on MMP activity after balloon angioplasty. Rats were divided into three groups: (1) control implants and tap water; (2) control implants and oral glucose, and (3) insulin implants (3 U/day) and oral glucose. Results: Gelatin zymography revealed that insulin reduced the gelatinolytic activity of pro-MMP-2 by 46% (p < 0.05), MMP-2 by 44% (p < 0.05) and MMP-9 by 51% (p < 0.05) compared to controls after arterial injury. Insulin also reduced mRNA levels of MMP-2 (p < 0.05) and MMP-9 (p < 0.05) and protein levels of MMP-2 (p < 0.05). In contrast, there were no significant changes in membrane-type 1 MMP protein and tissue inhibitors of MMP activity after insulin treatment. Thus, these results suggest a mechanism by which insulin inhibits SMC migration and supports a vasculoprotective role for insulin in vivo. |
| doi_str_mv | 10.1159/000351611 |
| format | Article |
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In vivo, the effect of insulin is mainly protective. Insulin treatment (3 U/day) decreases smooth muscle cell (SMC) migration and neointimal growth after carotid angioplasty in normal rats maintained at normoglycemia by oral glucose. SMC migration requires limited proteolysis of the extracellular matrix, which is mediated by matrix metalloproteinases (MMPs). In this study, we investigated the effects of normoglycemic hyperinsulinemia on MMP activity after balloon angioplasty. Rats were divided into three groups: (1) control implants and tap water; (2) control implants and oral glucose, and (3) insulin implants (3 U/day) and oral glucose. Results: Gelatin zymography revealed that insulin reduced the gelatinolytic activity of pro-MMP-2 by 46% (p < 0.05), MMP-2 by 44% (p < 0.05) and MMP-9 by 51% (p < 0.05) compared to controls after arterial injury. Insulin also reduced mRNA levels of MMP-2 (p < 0.05) and MMP-9 (p < 0.05) and protein levels of MMP-2 (p < 0.05). In contrast, there were no significant changes in membrane-type 1 MMP protein and tissue inhibitors of MMP activity after insulin treatment. Thus, these results suggest a mechanism by which insulin inhibits SMC migration and supports a vasculoprotective role for insulin in vivo.]]></description><identifier>ISSN: 1018-1172</identifier><identifier>EISSN: 1423-0135</identifier><identifier>DOI: 10.1159/000351611</identifier><identifier>PMID: 23988659</identifier><identifier>CODEN: JVREE9</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Administration, Oral ; Angioplasty, Balloon ; Animals ; Blood Glucose - drug effects ; Blood Glucose - metabolism ; Carotid Artery Injuries - drug therapy ; Carotid Artery Injuries - enzymology ; Carotid Artery Injuries - etiology ; Carotid Artery, Common - drug effects ; Carotid Artery, Common - enzymology ; Disease Models, Animal ; Down-Regulation ; Drug Implants ; Gene Expression Regulation, Enzymologic - drug effects ; Glucose - administration & dosage ; Insulin - administration & dosage ; Insulin - blood ; Insulin - pharmacology ; Male ; Matrix Metalloproteinase 14 - metabolism ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 2 - metabolism ; Matrix Metalloproteinase 9 - genetics ; Matrix Metalloproteinase 9 - metabolism ; Rats ; Rats, Sprague-Dawley ; Research Paper ; RNA, Messenger - metabolism ; Tissue Inhibitor of Metalloproteinases - metabolism ; Vascular System Injuries - drug therapy ; Vascular System Injuries - enzymology ; Vascular System Injuries - etiology</subject><ispartof>Journal of vascular research, 2013-01, Vol.50 (4), p.279-288</ispartof><rights>2013 S. Karger AG, Basel</rights><rights>Copyright © 2013 S. Karger AG, Basel.</rights><rights>Copyright (c) 2013 S. Karger AG, Basel</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c388t-a56fd9fd6c3e8f7b3b8d38fbb1271be5f41d880bb79ae8b8bd72a4614b487d003</citedby><cites>FETCH-LOGICAL-c388t-a56fd9fd6c3e8f7b3b8d38fbb1271be5f41d880bb79ae8b8bd72a4614b487d003</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,782,786,2433,27933,27934</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23988659$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Guo, June</creatorcontrib><creatorcontrib>Dhaliwall, Jiwanjeet K.</creatorcontrib><creatorcontrib>Chan, Kalam K.</creatorcontrib><creatorcontrib>Ghanim, Husam</creatorcontrib><creatorcontrib>Al Koudsi, Nael</creatorcontrib><creatorcontrib>Lam, Loretta</creatorcontrib><creatorcontrib>Madadi, Golnaz</creatorcontrib><creatorcontrib>Dandona, Paresh</creatorcontrib><creatorcontrib>Giacca, Adria</creatorcontrib><creatorcontrib>Bendeck, Michelle P.</creatorcontrib><title>In vivo Effect of Insulin to Decrease Matrix Metalloproteinase-2 and -9 Activity after Arterial Injury</title><title>Journal of vascular research</title><addtitle>J Vasc Res</addtitle><description><![CDATA[In vitro, insulin has both growth-promoting and vasculoprotective effects. In vivo, the effect of insulin is mainly protective. Insulin treatment (3 U/day) decreases smooth muscle cell (SMC) migration and neointimal growth after carotid angioplasty in normal rats maintained at normoglycemia by oral glucose. SMC migration requires limited proteolysis of the extracellular matrix, which is mediated by matrix metalloproteinases (MMPs). In this study, we investigated the effects of normoglycemic hyperinsulinemia on MMP activity after balloon angioplasty. Rats were divided into three groups: (1) control implants and tap water; (2) control implants and oral glucose, and (3) insulin implants (3 U/day) and oral glucose. Results: Gelatin zymography revealed that insulin reduced the gelatinolytic activity of pro-MMP-2 by 46% (p < 0.05), MMP-2 by 44% (p < 0.05) and MMP-9 by 51% (p < 0.05) compared to controls after arterial injury. Insulin also reduced mRNA levels of MMP-2 (p < 0.05) and MMP-9 (p < 0.05) and protein levels of MMP-2 (p < 0.05). In contrast, there were no significant changes in membrane-type 1 MMP protein and tissue inhibitors of MMP activity after insulin treatment. Thus, these results suggest a mechanism by which insulin inhibits SMC migration and supports a vasculoprotective role for insulin in vivo.]]></description><subject>Administration, Oral</subject><subject>Angioplasty, Balloon</subject><subject>Animals</subject><subject>Blood Glucose - drug effects</subject><subject>Blood Glucose - metabolism</subject><subject>Carotid Artery Injuries - drug therapy</subject><subject>Carotid Artery Injuries - enzymology</subject><subject>Carotid Artery Injuries - etiology</subject><subject>Carotid Artery, Common - drug effects</subject><subject>Carotid Artery, Common - enzymology</subject><subject>Disease Models, Animal</subject><subject>Down-Regulation</subject><subject>Drug Implants</subject><subject>Gene Expression Regulation, Enzymologic - drug effects</subject><subject>Glucose - administration & dosage</subject><subject>Insulin - administration & dosage</subject><subject>Insulin - blood</subject><subject>Insulin - pharmacology</subject><subject>Male</subject><subject>Matrix Metalloproteinase 14 - metabolism</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Matrix Metalloproteinase 9 - genetics</subject><subject>Matrix Metalloproteinase 9 - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Research Paper</subject><subject>RNA, Messenger - metabolism</subject><subject>Tissue Inhibitor of Metalloproteinases - metabolism</subject><subject>Vascular System Injuries - drug therapy</subject><subject>Vascular System Injuries - enzymology</subject><subject>Vascular System Injuries - etiology</subject><issn>1018-1172</issn><issn>1423-0135</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpt0M1LHDEYBvBQLPWrh96lBLzoYTRvMh_JcbFqV5SC2F6HZPJGsp2d2SaZxf3vG1m7h-IlCby_PLw8hHwBdgFQqUvGmKigBvhADqDkomAgqr38ZiALgIbvk8MYF4xBqWT9iexzoaSsK3VA3Hyga78e6bVz2CU6Ojof4tT7gaaRfsMuoI5IH3QK_oU-YNJ9P67CmNAPeVBwqgdLC0VnXfJrnzZUu4SBzkI-ve5z2mIKm2Py0ek-4ue3-4j8vLl-uvpe3P-4nV_N7otOSJkKXdXOKmfrTqB0jRFGWiGdMcAbMFi5EqyUzJhGaZRGGttwXdZQmlI2NrdwRM62uXnFPxPG1C597LDv9YDjFNvcjuJQi5pnevofXYxTGPJ2WQkuWKX4qzrfqi6MMQZ07Sr4pQ6bFlj7Wn67Kz_br2-Jk1mi3cl_bWdwsgW_dXjGsAO7_6fvju9-PW5Fu7JO_AXZl5Ks</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>Guo, June</creator><creator>Dhaliwall, Jiwanjeet K.</creator><creator>Chan, Kalam K.</creator><creator>Ghanim, Husam</creator><creator>Al Koudsi, Nael</creator><creator>Lam, Loretta</creator><creator>Madadi, Golnaz</creator><creator>Dandona, Paresh</creator><creator>Giacca, Adria</creator><creator>Bendeck, Michelle P.</creator><general>S. 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drug effects</topic><topic>Blood Glucose - metabolism</topic><topic>Carotid Artery Injuries - drug therapy</topic><topic>Carotid Artery Injuries - enzymology</topic><topic>Carotid Artery Injuries - etiology</topic><topic>Carotid Artery, Common - drug effects</topic><topic>Carotid Artery, Common - enzymology</topic><topic>Disease Models, Animal</topic><topic>Down-Regulation</topic><topic>Drug Implants</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Glucose - administration & dosage</topic><topic>Insulin - administration & dosage</topic><topic>Insulin - blood</topic><topic>Insulin - pharmacology</topic><topic>Male</topic><topic>Matrix Metalloproteinase 14 - metabolism</topic><topic>Matrix Metalloproteinase 2 - genetics</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Matrix Metalloproteinase 9 - genetics</topic><topic>Matrix Metalloproteinase 9 - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Research Paper</topic><topic>RNA, Messenger - 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Academic</collection><jtitle>Journal of vascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Guo, June</au><au>Dhaliwall, Jiwanjeet K.</au><au>Chan, Kalam K.</au><au>Ghanim, Husam</au><au>Al Koudsi, Nael</au><au>Lam, Loretta</au><au>Madadi, Golnaz</au><au>Dandona, Paresh</au><au>Giacca, Adria</au><au>Bendeck, Michelle P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vivo Effect of Insulin to Decrease Matrix Metalloproteinase-2 and -9 Activity after Arterial Injury</atitle><jtitle>Journal of vascular research</jtitle><addtitle>J Vasc Res</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>50</volume><issue>4</issue><spage>279</spage><epage>288</epage><pages>279-288</pages><issn>1018-1172</issn><eissn>1423-0135</eissn><coden>JVREE9</coden><abstract><![CDATA[In vitro, insulin has both growth-promoting and vasculoprotective effects. In vivo, the effect of insulin is mainly protective. Insulin treatment (3 U/day) decreases smooth muscle cell (SMC) migration and neointimal growth after carotid angioplasty in normal rats maintained at normoglycemia by oral glucose. SMC migration requires limited proteolysis of the extracellular matrix, which is mediated by matrix metalloproteinases (MMPs). In this study, we investigated the effects of normoglycemic hyperinsulinemia on MMP activity after balloon angioplasty. Rats were divided into three groups: (1) control implants and tap water; (2) control implants and oral glucose, and (3) insulin implants (3 U/day) and oral glucose. Results: Gelatin zymography revealed that insulin reduced the gelatinolytic activity of pro-MMP-2 by 46% (p < 0.05), MMP-2 by 44% (p < 0.05) and MMP-9 by 51% (p < 0.05) compared to controls after arterial injury. Insulin also reduced mRNA levels of MMP-2 (p < 0.05) and MMP-9 (p < 0.05) and protein levels of MMP-2 (p < 0.05). In contrast, there were no significant changes in membrane-type 1 MMP protein and tissue inhibitors of MMP activity after insulin treatment. Thus, these results suggest a mechanism by which insulin inhibits SMC migration and supports a vasculoprotective role for insulin in vivo.]]></abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>23988659</pmid><doi>10.1159/000351611</doi><tpages>10</tpages></addata></record> |
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| subjects | Administration, Oral Angioplasty, Balloon Animals Blood Glucose - drug effects Blood Glucose - metabolism Carotid Artery Injuries - drug therapy Carotid Artery Injuries - enzymology Carotid Artery Injuries - etiology Carotid Artery, Common - drug effects Carotid Artery, Common - enzymology Disease Models, Animal Down-Regulation Drug Implants Gene Expression Regulation, Enzymologic - drug effects Glucose - administration & dosage Insulin - administration & dosage Insulin - blood Insulin - pharmacology Male Matrix Metalloproteinase 14 - metabolism Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 2 - metabolism Matrix Metalloproteinase 9 - genetics Matrix Metalloproteinase 9 - metabolism Rats Rats, Sprague-Dawley Research Paper RNA, Messenger - metabolism Tissue Inhibitor of Metalloproteinases - metabolism Vascular System Injuries - drug therapy Vascular System Injuries - enzymology Vascular System Injuries - etiology |
| title | In vivo Effect of Insulin to Decrease Matrix Metalloproteinase-2 and -9 Activity after Arterial Injury |
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