AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells
The liver is one of the major target organs of insulin in which the expression of insulin receptor is abundant. We analyzed the effect of AICAR, an AMPK activator, on the expression of insulin receptor in a human hepatoma cell line, HepG2 cells. AICAR treatment for 48 h significantly decreased the e...
Gespeichert in:
| Veröffentlicht in: | Biochemical and biophysical research communications 2005-03, Vol.328 (2), p.449-454 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 454 |
|---|---|
| container_issue | 2 |
| container_start_page | 449 |
| container_title | Biochemical and biophysical research communications |
| container_volume | 328 |
| creator | Nakamaru, Kazuhiko Matsumoto, Kazuya Taguchi, Tetsuya Suefuji, Mihoshi Murata, Yusuke Igata, Motoyuki Kawashima, Junji Kondo, Tatsuya Motoshima, Hiroyuki Tsuruzoe, Kaku Miyamura, Nobuhiro Toyonaga, Tetsushi Araki, Eiichi |
| description | The liver is one of the major target organs of insulin in which the expression of insulin receptor is abundant. We analyzed the effect of AICAR, an AMPK activator, on the expression of insulin receptor in a human hepatoma cell line, HepG2 cells. AICAR treatment for 48
h significantly decreased the expression of the insulin receptor protein in a dose-dependent manner, however, this same effect of AICAR was not observed in either 3T3-L1 adipocytes or CHO cells. The expression of insulin receptor mRNA also decreased after AICAR treatment. In addition, the transcriptional activity of the insulin receptor gene promoter investigated with a luciferase assay was down-regulated by AICAR treatment. Dipyridamole, an adenosine transporter inhibitor, and 5′-amino-5′-deoxyadenosine, an adenosine kinase inhibitor, blocked the effect of AICAR on the down-regulation of the insulin receptor protein, mRNA, and promoter activity. Our findings suggest, for the first time, that AMPK activation could reduce the expression of insulin receptor, at least in part, by a down-regulation of the transcriptional level, and this effect may be liver specific. |
| doi_str_mv | 10.1016/j.bbrc.2005.01.004 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67410517</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0006291X05000227</els_id><sourcerecordid>67410517</sourcerecordid><originalsourceid>FETCH-LOGICAL-c420t-a7e41f9950bc144cc47ff5843afab4e10721b3310ca7e6f3260ccca0265faa4f3</originalsourceid><addsrcrecordid>eNp9kMFO3DAQhi3UqizQF-CAfOqJpDOO4xCJywq1UIkKhKjUm-U449ZLNgl2Au3b42hX6q0nS55vfv3zMXaKkCOg-rzJmybYXACUOWAOIA_YCqGGTCDId2wFACoTNf48ZEcxbgAQpao_sEMsVS0LdbFiYf3tav1wzk3PjZ38i5mGwAfH19_vs_0HtXwMw0S-50--N5HOeTu89lmgX3OXxpFPv4n7Ps5dQgJZGpcQ-jMGitEPfZrxGxqvBbfUdfGEvXemi_Rx_x6zH1-_PF7dZLd316nMbWalgCkzFUl0dV1CY1FKa2XlXHkhC-NMIwmhEtgUBYJNpHKFUGCtNSBU6YyRrjhmn3a5qf3zTHHSWx-XBqanYY5aVRKhxCqBYgfaMMQYyOkx-K0JfzWCXkzrjV5M68W0BtTJdFo626fPzZbafyt7tQm43AGUbnzxFHS0nnpLrU-OJt0O_n_5b16Wj_Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67410517</pqid></control><display><type>article</type><title>AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><creator>Nakamaru, Kazuhiko ; Matsumoto, Kazuya ; Taguchi, Tetsuya ; Suefuji, Mihoshi ; Murata, Yusuke ; Igata, Motoyuki ; Kawashima, Junji ; Kondo, Tatsuya ; Motoshima, Hiroyuki ; Tsuruzoe, Kaku ; Miyamura, Nobuhiro ; Toyonaga, Tetsushi ; Araki, Eiichi</creator><creatorcontrib>Nakamaru, Kazuhiko ; Matsumoto, Kazuya ; Taguchi, Tetsuya ; Suefuji, Mihoshi ; Murata, Yusuke ; Igata, Motoyuki ; Kawashima, Junji ; Kondo, Tatsuya ; Motoshima, Hiroyuki ; Tsuruzoe, Kaku ; Miyamura, Nobuhiro ; Toyonaga, Tetsushi ; Araki, Eiichi</creatorcontrib><description>The liver is one of the major target organs of insulin in which the expression of insulin receptor is abundant. We analyzed the effect of AICAR, an AMPK activator, on the expression of insulin receptor in a human hepatoma cell line, HepG2 cells. AICAR treatment for 48
h significantly decreased the expression of the insulin receptor protein in a dose-dependent manner, however, this same effect of AICAR was not observed in either 3T3-L1 adipocytes or CHO cells. The expression of insulin receptor mRNA also decreased after AICAR treatment. In addition, the transcriptional activity of the insulin receptor gene promoter investigated with a luciferase assay was down-regulated by AICAR treatment. Dipyridamole, an adenosine transporter inhibitor, and 5′-amino-5′-deoxyadenosine, an adenosine kinase inhibitor, blocked the effect of AICAR on the down-regulation of the insulin receptor protein, mRNA, and promoter activity. Our findings suggest, for the first time, that AMPK activation could reduce the expression of insulin receptor, at least in part, by a down-regulation of the transcriptional level, and this effect may be liver specific.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2005.01.004</identifier><identifier>PMID: 15694368</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>3T3-L1 Cells ; AICAR ; Aminoimidazole Carboxamide - analogs & derivatives ; Aminoimidazole Carboxamide - pharmacology ; AMP-Activated Protein Kinases ; AMPK ; Animals ; Carcinoma, Hepatocellular - metabolism ; Cell Line, Tumor ; CHO Cells ; Cricetinae ; Cricetulus ; Diabetes mellitus ; Dose-Response Relationship, Drug ; Down-Regulation - drug effects ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; Insulin receptor gene ; Mice ; Multienzyme Complexes - antagonists & inhibitors ; Promoter ; Protein-Serine-Threonine Kinases - antagonists & inhibitors ; Receptor, Insulin - metabolism ; Ribonucleotides - pharmacology ; Transcription factor</subject><ispartof>Biochemical and biophysical research communications, 2005-03, Vol.328 (2), p.449-454</ispartof><rights>2005 Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c420t-a7e41f9950bc144cc47ff5843afab4e10721b3310ca7e6f3260ccca0265faa4f3</citedby><cites>FETCH-LOGICAL-c420t-a7e41f9950bc144cc47ff5843afab4e10721b3310ca7e6f3260ccca0265faa4f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2005.01.004$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15694368$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nakamaru, Kazuhiko</creatorcontrib><creatorcontrib>Matsumoto, Kazuya</creatorcontrib><creatorcontrib>Taguchi, Tetsuya</creatorcontrib><creatorcontrib>Suefuji, Mihoshi</creatorcontrib><creatorcontrib>Murata, Yusuke</creatorcontrib><creatorcontrib>Igata, Motoyuki</creatorcontrib><creatorcontrib>Kawashima, Junji</creatorcontrib><creatorcontrib>Kondo, Tatsuya</creatorcontrib><creatorcontrib>Motoshima, Hiroyuki</creatorcontrib><creatorcontrib>Tsuruzoe, Kaku</creatorcontrib><creatorcontrib>Miyamura, Nobuhiro</creatorcontrib><creatorcontrib>Toyonaga, Tetsushi</creatorcontrib><creatorcontrib>Araki, Eiichi</creatorcontrib><title>AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>The liver is one of the major target organs of insulin in which the expression of insulin receptor is abundant. We analyzed the effect of AICAR, an AMPK activator, on the expression of insulin receptor in a human hepatoma cell line, HepG2 cells. AICAR treatment for 48
h significantly decreased the expression of the insulin receptor protein in a dose-dependent manner, however, this same effect of AICAR was not observed in either 3T3-L1 adipocytes or CHO cells. The expression of insulin receptor mRNA also decreased after AICAR treatment. In addition, the transcriptional activity of the insulin receptor gene promoter investigated with a luciferase assay was down-regulated by AICAR treatment. Dipyridamole, an adenosine transporter inhibitor, and 5′-amino-5′-deoxyadenosine, an adenosine kinase inhibitor, blocked the effect of AICAR on the down-regulation of the insulin receptor protein, mRNA, and promoter activity. Our findings suggest, for the first time, that AMPK activation could reduce the expression of insulin receptor, at least in part, by a down-regulation of the transcriptional level, and this effect may be liver specific.</description><subject>3T3-L1 Cells</subject><subject>AICAR</subject><subject>Aminoimidazole Carboxamide - analogs & derivatives</subject><subject>Aminoimidazole Carboxamide - pharmacology</subject><subject>AMP-Activated Protein Kinases</subject><subject>AMPK</subject><subject>Animals</subject><subject>Carcinoma, Hepatocellular - metabolism</subject><subject>Cell Line, Tumor</subject><subject>CHO Cells</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Diabetes mellitus</subject><subject>Dose-Response Relationship, Drug</subject><subject>Down-Regulation - drug effects</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>Insulin receptor gene</subject><subject>Mice</subject><subject>Multienzyme Complexes - antagonists & inhibitors</subject><subject>Promoter</subject><subject>Protein-Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Receptor, Insulin - metabolism</subject><subject>Ribonucleotides - pharmacology</subject><subject>Transcription factor</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMFO3DAQhi3UqizQF-CAfOqJpDOO4xCJywq1UIkKhKjUm-U449ZLNgl2Au3b42hX6q0nS55vfv3zMXaKkCOg-rzJmybYXACUOWAOIA_YCqGGTCDId2wFACoTNf48ZEcxbgAQpao_sEMsVS0LdbFiYf3tav1wzk3PjZ38i5mGwAfH19_vs_0HtXwMw0S-50--N5HOeTu89lmgX3OXxpFPv4n7Ps5dQgJZGpcQ-jMGitEPfZrxGxqvBbfUdfGEvXemi_Rx_x6zH1-_PF7dZLd316nMbWalgCkzFUl0dV1CY1FKa2XlXHkhC-NMIwmhEtgUBYJNpHKFUGCtNSBU6YyRrjhmn3a5qf3zTHHSWx-XBqanYY5aVRKhxCqBYgfaMMQYyOkx-K0JfzWCXkzrjV5M68W0BtTJdFo626fPzZbafyt7tQm43AGUbnzxFHS0nnpLrU-OJt0O_n_5b16Wj_Q</recordid><startdate>20050311</startdate><enddate>20050311</enddate><creator>Nakamaru, Kazuhiko</creator><creator>Matsumoto, Kazuya</creator><creator>Taguchi, Tetsuya</creator><creator>Suefuji, Mihoshi</creator><creator>Murata, Yusuke</creator><creator>Igata, Motoyuki</creator><creator>Kawashima, Junji</creator><creator>Kondo, Tatsuya</creator><creator>Motoshima, Hiroyuki</creator><creator>Tsuruzoe, Kaku</creator><creator>Miyamura, Nobuhiro</creator><creator>Toyonaga, Tetsushi</creator><creator>Araki, Eiichi</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>20050311</creationdate><title>AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells</title><author>Nakamaru, Kazuhiko ; Matsumoto, Kazuya ; Taguchi, Tetsuya ; Suefuji, Mihoshi ; Murata, Yusuke ; Igata, Motoyuki ; Kawashima, Junji ; Kondo, Tatsuya ; Motoshima, Hiroyuki ; Tsuruzoe, Kaku ; Miyamura, Nobuhiro ; Toyonaga, Tetsushi ; Araki, Eiichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c420t-a7e41f9950bc144cc47ff5843afab4e10721b3310ca7e6f3260ccca0265faa4f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>3T3-L1 Cells</topic><topic>AICAR</topic><topic>Aminoimidazole Carboxamide - analogs & derivatives</topic><topic>Aminoimidazole Carboxamide - pharmacology</topic><topic>AMP-Activated Protein Kinases</topic><topic>AMPK</topic><topic>Animals</topic><topic>Carcinoma, Hepatocellular - metabolism</topic><topic>Cell Line, Tumor</topic><topic>CHO Cells</topic><topic>Cricetinae</topic><topic>Cricetulus</topic><topic>Diabetes mellitus</topic><topic>Dose-Response Relationship, Drug</topic><topic>Down-Regulation - drug effects</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>Insulin receptor gene</topic><topic>Mice</topic><topic>Multienzyme Complexes - antagonists & inhibitors</topic><topic>Promoter</topic><topic>Protein-Serine-Threonine Kinases - antagonists & inhibitors</topic><topic>Receptor, Insulin - metabolism</topic><topic>Ribonucleotides - pharmacology</topic><topic>Transcription factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nakamaru, Kazuhiko</creatorcontrib><creatorcontrib>Matsumoto, Kazuya</creatorcontrib><creatorcontrib>Taguchi, Tetsuya</creatorcontrib><creatorcontrib>Suefuji, Mihoshi</creatorcontrib><creatorcontrib>Murata, Yusuke</creatorcontrib><creatorcontrib>Igata, Motoyuki</creatorcontrib><creatorcontrib>Kawashima, Junji</creatorcontrib><creatorcontrib>Kondo, Tatsuya</creatorcontrib><creatorcontrib>Motoshima, Hiroyuki</creatorcontrib><creatorcontrib>Tsuruzoe, Kaku</creatorcontrib><creatorcontrib>Miyamura, Nobuhiro</creatorcontrib><creatorcontrib>Toyonaga, Tetsushi</creatorcontrib><creatorcontrib>Araki, Eiichi</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>Nakamaru, Kazuhiko</au><au>Matsumoto, Kazuya</au><au>Taguchi, Tetsuya</au><au>Suefuji, Mihoshi</au><au>Murata, Yusuke</au><au>Igata, Motoyuki</au><au>Kawashima, Junji</au><au>Kondo, Tatsuya</au><au>Motoshima, Hiroyuki</au><au>Tsuruzoe, Kaku</au><au>Miyamura, Nobuhiro</au><au>Toyonaga, Tetsushi</au><au>Araki, Eiichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2005-03-11</date><risdate>2005</risdate><volume>328</volume><issue>2</issue><spage>449</spage><epage>454</epage><pages>449-454</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>The liver is one of the major target organs of insulin in which the expression of insulin receptor is abundant. We analyzed the effect of AICAR, an AMPK activator, on the expression of insulin receptor in a human hepatoma cell line, HepG2 cells. AICAR treatment for 48
h significantly decreased the expression of the insulin receptor protein in a dose-dependent manner, however, this same effect of AICAR was not observed in either 3T3-L1 adipocytes or CHO cells. The expression of insulin receptor mRNA also decreased after AICAR treatment. In addition, the transcriptional activity of the insulin receptor gene promoter investigated with a luciferase assay was down-regulated by AICAR treatment. Dipyridamole, an adenosine transporter inhibitor, and 5′-amino-5′-deoxyadenosine, an adenosine kinase inhibitor, blocked the effect of AICAR on the down-regulation of the insulin receptor protein, mRNA, and promoter activity. Our findings suggest, for the first time, that AMPK activation could reduce the expression of insulin receptor, at least in part, by a down-regulation of the transcriptional level, and this effect may be liver specific.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15694368</pmid><doi>10.1016/j.bbrc.2005.01.004</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-291X |
| ispartof | Biochemical and biophysical research communications, 2005-03, Vol.328 (2), p.449-454 |
| issn | 0006-291X 1090-2104 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67410517 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | 3T3-L1 Cells AICAR Aminoimidazole Carboxamide - analogs & derivatives Aminoimidazole Carboxamide - pharmacology AMP-Activated Protein Kinases AMPK Animals Carcinoma, Hepatocellular - metabolism Cell Line, Tumor CHO Cells Cricetinae Cricetulus Diabetes mellitus Dose-Response Relationship, Drug Down-Regulation - drug effects Gene Expression Regulation, Neoplastic - drug effects Humans Insulin receptor gene Mice Multienzyme Complexes - antagonists & inhibitors Promoter Protein-Serine-Threonine Kinases - antagonists & inhibitors Receptor, Insulin - metabolism Ribonucleotides - pharmacology Transcription factor |
| title | AICAR, an activator of AMP-activated protein kinase, down-regulates the insulin receptor expression in HepG2 cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T21%3A40%3A14IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=AICAR,%20an%20activator%20of%20AMP-activated%20protein%20kinase,%20down-regulates%20the%20insulin%20receptor%20expression%20in%20HepG2%20cells&rft.jtitle=Biochemical%20and%20biophysical%20research%20communications&rft.au=Nakamaru,%20Kazuhiko&rft.date=2005-03-11&rft.volume=328&rft.issue=2&rft.spage=449&rft.epage=454&rft.pages=449-454&rft.issn=0006-291X&rft.eissn=1090-2104&rft_id=info:doi/10.1016/j.bbrc.2005.01.004&rft_dat=%3Cproquest_cross%3E67410517%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=67410517&rft_id=info:pmid/15694368&rft_els_id=S0006291X05000227&rfr_iscdi=true |