Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells
Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells Ha-il Kim 1 , Ji-Young Cha 1 , So-Youn Kim 1 , Jae-woo Kim 1 , Kyung Jin Roh 2 , Je-Kyung Seong 2 , Nam Taek Lee 3 , Kang-Yell Choi 1 , Kyung-Sup Kim 1 and Yong-ho Ahn 1 1 Department of Biochemistry and...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2002-03, Vol.51 (3), p.676-685 |
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| creator | KIM, Ha-Il CHA, Ji-Young KIM, So-Youn KIM, Jae-Woo KYUNG JIN ROH SEONG, Je-Kyung LEE, Nam Taek KANG-YELL CHOI KIM, Kyung-Sup AHNL, Yong-Ho |
| description | Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells
Ha-il Kim 1 ,
Ji-Young Cha 1 ,
So-Youn Kim 1 ,
Jae-woo Kim 1 ,
Kyung Jin Roh 2 ,
Je-Kyung Seong 2 ,
Nam Taek Lee 3 ,
Kang-Yell Choi 1 ,
Kyung-Sup Kim 1 and
Yong-ho Ahn 1
1 Department of Biochemistry and Molecular Biology, the Institute of Genetic Science, Yonsei University College of Medicine,
Seoul, Korea
2 Department of Laboratory Animal Medicine, Medical Research Center, Yonsei, College of Medicine, Seoul, Korea
3 Department of Chemistry, Korea Military Academy, Seoul, Korea
Abstract
Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-γ (PPAR-γ), improve peripheral insulin
sensitivity and glucose-stimulated insulin secretion in pancreatic β-cells. To explore the role of PPAR-γ in glucose sensing
of β-cells, we have dissected the β-cell-specific glucokinase (βGK) promoter, which constitutes glucose-sensing apparatus
in pancreatic β-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter. The βGK-PPRE is
located in the region between +47 and +68 bp. PPAR-γ/retinoid X receptor-α heterodimer binds to the element and activates
the βGK promoter. The βGK promoter lacking or having mutations in PPRE cannot be activated by PPAR-γ. PPAR-γ activates the
βGK promoter in β-cells as well as non-β-cells. Furthermore, troglitazone increases endogenous GK expression and its enzyme
activity in β-cell lines. These results indicate that PPAR-γ can regulate GK expression in β-cells. Taking these results together
with our previous work, we conclude that PPAR-γ regulates gene expression of glucose-sensing apparatus and thereby improves
glucose-sensing ability of β-cells, contributing to the restoration of β-cell function in type 2 diabetic subjects by troglitazone.
Footnotes
Address correspondence and reprint requests to Yong-ho Ahn, Department of Biochemistry and Molecular Biology, Yonsei University
College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. E-mail: yha111{at}yumc.yonsei.ac.kr .
Received for publication 6 September 2001 and accepted in revised form 26 November 2001.
H.-I.K. and J.-Y.C. contributed equally to this work.
βGK, β-cell-specific GK; DMEM, Dulbecco’s modified Eagle’s medium; EMSA, electrophoretic mobility shift assay; FBS, fetal
bovine serum; GK, glucokinase; GSIS, glucose-stimulated insulin secretion; LGK, rat liver-specific GK; MODY, maturity-onset
diabetes of the young |
| doi_str_mv | 10.2337/diabetes.51.3.676 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_gale_infotracacademiconefile_A84209409</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A84209409</galeid><sourcerecordid>A84209409</sourcerecordid><originalsourceid>FETCH-LOGICAL-c540t-b2cd95d274c2035fb752fae8bf0f660c185d915fefc5513afba19f977fdc3bd83</originalsourceid><addsrcrecordid>eNpt0d2KEzEUB_BBFLeuPoA3MgiCiFPzMUkml6WsVSi4iAvehUzmZDZrOqnJjNbX0vfYZzKllbK45CJw8js5Cf-ieI7RnFAq3nVOtzBCmjM8p3Mu-INihiWVFSXi68NihhAmFRZSnBVPUrpBCPG8HhdnGDeCcM5nRXsJMexcChvty8sYvLMQ9RhitTCj-6FH6MrPYGC7L93-Ka-2EfrJ53oqV34y4ZsbdIJyBQOUF7t8mpILQ-mG8vZ3tQTv09PikdU-wbPjfl5cvb_4svxQrT-tPi4X68qwGo1VS0wnWUdEbQiizLaCEauhaS2ynCODG9ZJzCxYwxim2rYaSyuFsJ2hbdfQ8-Ll4d5tDN8nSKO6CVMc8khFMK9FLQnP6O0B9dqDcoMNY9Smz6-P2ocBrMvlRVMTJGskM6_u4Xl1sHHmPv_6js9khN3Y6ykl1azWdyg-UBNDShGs2ka30fGXwkjt41X_4lUMK6pyvLnnxfGLU7uB7tRxzDODV0egk9HeRj0Yl06OMswl27s3B3ft-uufLsJp2P9T_wK5SMB-</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>216474926</pqid></control><display><type>article</type><title>Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>KIM, Ha-Il ; CHA, Ji-Young ; KIM, So-Youn ; KIM, Jae-Woo ; KYUNG JIN ROH ; SEONG, Je-Kyung ; LEE, Nam Taek ; KANG-YELL CHOI ; KIM, Kyung-Sup ; AHNL, Yong-Ho</creator><creatorcontrib>KIM, Ha-Il ; CHA, Ji-Young ; KIM, So-Youn ; KIM, Jae-Woo ; KYUNG JIN ROH ; SEONG, Je-Kyung ; LEE, Nam Taek ; KANG-YELL CHOI ; KIM, Kyung-Sup ; AHNL, Yong-Ho</creatorcontrib><description>Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells
Ha-il Kim 1 ,
Ji-Young Cha 1 ,
So-Youn Kim 1 ,
Jae-woo Kim 1 ,
Kyung Jin Roh 2 ,
Je-Kyung Seong 2 ,
Nam Taek Lee 3 ,
Kang-Yell Choi 1 ,
Kyung-Sup Kim 1 and
Yong-ho Ahn 1
1 Department of Biochemistry and Molecular Biology, the Institute of Genetic Science, Yonsei University College of Medicine,
Seoul, Korea
2 Department of Laboratory Animal Medicine, Medical Research Center, Yonsei, College of Medicine, Seoul, Korea
3 Department of Chemistry, Korea Military Academy, Seoul, Korea
Abstract
Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-γ (PPAR-γ), improve peripheral insulin
sensitivity and glucose-stimulated insulin secretion in pancreatic β-cells. To explore the role of PPAR-γ in glucose sensing
of β-cells, we have dissected the β-cell-specific glucokinase (βGK) promoter, which constitutes glucose-sensing apparatus
in pancreatic β-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter. The βGK-PPRE is
located in the region between +47 and +68 bp. PPAR-γ/retinoid X receptor-α heterodimer binds to the element and activates
the βGK promoter. The βGK promoter lacking or having mutations in PPRE cannot be activated by PPAR-γ. PPAR-γ activates the
βGK promoter in β-cells as well as non-β-cells. Furthermore, troglitazone increases endogenous GK expression and its enzyme
activity in β-cell lines. These results indicate that PPAR-γ can regulate GK expression in β-cells. Taking these results together
with our previous work, we conclude that PPAR-γ regulates gene expression of glucose-sensing apparatus and thereby improves
glucose-sensing ability of β-cells, contributing to the restoration of β-cell function in type 2 diabetic subjects by troglitazone.
Footnotes
Address correspondence and reprint requests to Yong-ho Ahn, Department of Biochemistry and Molecular Biology, Yonsei University
College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. E-mail: yha111{at}yumc.yonsei.ac.kr .
Received for publication 6 September 2001 and accepted in revised form 26 November 2001.
H.-I.K. and J.-Y.C. contributed equally to this work.
βGK, β-cell-specific GK; DMEM, Dulbecco’s modified Eagle’s medium; EMSA, electrophoretic mobility shift assay; FBS, fetal
bovine serum; GK, glucokinase; GSIS, glucose-stimulated insulin secretion; LGK, rat liver-specific GK; MODY, maturity-onset
diabetes of the young; PDX-1, pancreatic duodenal homeobox gene-1; PPAR, peroxisomal proliferator-activated receptor; PPRE,
peroxisomal proliferator response element; RPA, RNase protection assay; RXR-α, retinoid X receptor-α; TZD, thiazolidinedione.
DIABETES</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.51.3.676</identifier><identifier>PMID: 11872666</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Animals ; Biological and medical sciences ; Cell Line ; Cell research ; Chromans - pharmacology ; Diabetes ; Dimerization ; DNA - metabolism ; Enzyme Activation - drug effects ; Evaluation ; Gene expression ; Gene Expression - drug effects ; Glucokinase - genetics ; Glucose ; Hypoglycemic Agents - pharmacology ; Insulin ; Islets of Langerhans - enzymology ; Mice ; Mutagenesis, Site-Directed ; Peroxisomes ; Physiological aspects ; Plasmids ; Promoter Regions, Genetic ; Rats ; Receptors, Cytoplasmic and Nuclear - metabolism ; Receptors, Cytoplasmic and Nuclear - physiology ; Receptors, Retinoic Acid - metabolism ; Response Elements ; Retinoid X Receptors ; Thiazoles - pharmacology ; Thiazolidinediones ; Transcription Factors - metabolism ; Transcription Factors - pharmacology ; Transcription Factors - physiology ; Transcriptional Activation ; Transfection ; Troglitazone</subject><ispartof>Diabetes (New York, N.Y.), 2002-03, Vol.51 (3), p.676-685</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2002 American Diabetes Association</rights><rights>Copyright American Diabetes Association Mar 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-b2cd95d274c2035fb752fae8bf0f660c185d915fefc5513afba19f977fdc3bd83</citedby><cites>FETCH-LOGICAL-c540t-b2cd95d274c2035fb752fae8bf0f660c185d915fefc5513afba19f977fdc3bd83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13516956$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11872666$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>KIM, Ha-Il</creatorcontrib><creatorcontrib>CHA, Ji-Young</creatorcontrib><creatorcontrib>KIM, So-Youn</creatorcontrib><creatorcontrib>KIM, Jae-Woo</creatorcontrib><creatorcontrib>KYUNG JIN ROH</creatorcontrib><creatorcontrib>SEONG, Je-Kyung</creatorcontrib><creatorcontrib>LEE, Nam Taek</creatorcontrib><creatorcontrib>KANG-YELL CHOI</creatorcontrib><creatorcontrib>KIM, Kyung-Sup</creatorcontrib><creatorcontrib>AHNL, Yong-Ho</creatorcontrib><title>Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells
Ha-il Kim 1 ,
Ji-Young Cha 1 ,
So-Youn Kim 1 ,
Jae-woo Kim 1 ,
Kyung Jin Roh 2 ,
Je-Kyung Seong 2 ,
Nam Taek Lee 3 ,
Kang-Yell Choi 1 ,
Kyung-Sup Kim 1 and
Yong-ho Ahn 1
1 Department of Biochemistry and Molecular Biology, the Institute of Genetic Science, Yonsei University College of Medicine,
Seoul, Korea
2 Department of Laboratory Animal Medicine, Medical Research Center, Yonsei, College of Medicine, Seoul, Korea
3 Department of Chemistry, Korea Military Academy, Seoul, Korea
Abstract
Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-γ (PPAR-γ), improve peripheral insulin
sensitivity and glucose-stimulated insulin secretion in pancreatic β-cells. To explore the role of PPAR-γ in glucose sensing
of β-cells, we have dissected the β-cell-specific glucokinase (βGK) promoter, which constitutes glucose-sensing apparatus
in pancreatic β-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter. The βGK-PPRE is
located in the region between +47 and +68 bp. PPAR-γ/retinoid X receptor-α heterodimer binds to the element and activates
the βGK promoter. The βGK promoter lacking or having mutations in PPRE cannot be activated by PPAR-γ. PPAR-γ activates the
βGK promoter in β-cells as well as non-β-cells. Furthermore, troglitazone increases endogenous GK expression and its enzyme
activity in β-cell lines. These results indicate that PPAR-γ can regulate GK expression in β-cells. Taking these results together
with our previous work, we conclude that PPAR-γ regulates gene expression of glucose-sensing apparatus and thereby improves
glucose-sensing ability of β-cells, contributing to the restoration of β-cell function in type 2 diabetic subjects by troglitazone.
Footnotes
Address correspondence and reprint requests to Yong-ho Ahn, Department of Biochemistry and Molecular Biology, Yonsei University
College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. E-mail: yha111{at}yumc.yonsei.ac.kr .
Received for publication 6 September 2001 and accepted in revised form 26 November 2001.
H.-I.K. and J.-Y.C. contributed equally to this work.
βGK, β-cell-specific GK; DMEM, Dulbecco’s modified Eagle’s medium; EMSA, electrophoretic mobility shift assay; FBS, fetal
bovine serum; GK, glucokinase; GSIS, glucose-stimulated insulin secretion; LGK, rat liver-specific GK; MODY, maturity-onset
diabetes of the young; PDX-1, pancreatic duodenal homeobox gene-1; PPAR, peroxisomal proliferator-activated receptor; PPRE,
peroxisomal proliferator response element; RPA, RNase protection assay; RXR-α, retinoid X receptor-α; TZD, thiazolidinedione.
DIABETES</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Cell research</subject><subject>Chromans - pharmacology</subject><subject>Diabetes</subject><subject>Dimerization</subject><subject>DNA - metabolism</subject><subject>Enzyme Activation - drug effects</subject><subject>Evaluation</subject><subject>Gene expression</subject><subject>Gene Expression - drug effects</subject><subject>Glucokinase - genetics</subject><subject>Glucose</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin</subject><subject>Islets of Langerhans - enzymology</subject><subject>Mice</subject><subject>Mutagenesis, Site-Directed</subject><subject>Peroxisomes</subject><subject>Physiological aspects</subject><subject>Plasmids</subject><subject>Promoter Regions, Genetic</subject><subject>Rats</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>Receptors, Cytoplasmic and Nuclear - physiology</subject><subject>Receptors, Retinoic Acid - metabolism</subject><subject>Response Elements</subject><subject>Retinoid X Receptors</subject><subject>Thiazoles - pharmacology</subject><subject>Thiazolidinediones</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription Factors - pharmacology</subject><subject>Transcription Factors - physiology</subject><subject>Transcriptional Activation</subject><subject>Transfection</subject><subject>Troglitazone</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpt0d2KEzEUB_BBFLeuPoA3MgiCiFPzMUkml6WsVSi4iAvehUzmZDZrOqnJjNbX0vfYZzKllbK45CJw8js5Cf-ieI7RnFAq3nVOtzBCmjM8p3Mu-INihiWVFSXi68NihhAmFRZSnBVPUrpBCPG8HhdnGDeCcM5nRXsJMexcChvty8sYvLMQ9RhitTCj-6FH6MrPYGC7L93-Ka-2EfrJ53oqV34y4ZsbdIJyBQOUF7t8mpILQ-mG8vZ3tQTv09PikdU-wbPjfl5cvb_4svxQrT-tPi4X68qwGo1VS0wnWUdEbQiizLaCEauhaS2ynCODG9ZJzCxYwxim2rYaSyuFsJ2hbdfQ8-Ll4d5tDN8nSKO6CVMc8khFMK9FLQnP6O0B9dqDcoMNY9Smz6-P2ocBrMvlRVMTJGskM6_u4Xl1sHHmPv_6js9khN3Y6ykl1azWdyg-UBNDShGs2ka30fGXwkjt41X_4lUMK6pyvLnnxfGLU7uB7tRxzDODV0egk9HeRj0Yl06OMswl27s3B3ft-uufLsJp2P9T_wK5SMB-</recordid><startdate>20020301</startdate><enddate>20020301</enddate><creator>KIM, Ha-Il</creator><creator>CHA, Ji-Young</creator><creator>KIM, So-Youn</creator><creator>KIM, Jae-Woo</creator><creator>KYUNG JIN ROH</creator><creator>SEONG, Je-Kyung</creator><creator>LEE, Nam Taek</creator><creator>KANG-YELL CHOI</creator><creator>KIM, Kyung-Sup</creator><creator>AHNL, Yong-Ho</creator><general>American Diabetes Association</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>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQGLB</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope></search><sort><creationdate>20020301</creationdate><title>Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells</title><author>KIM, Ha-Il ; CHA, Ji-Young ; KIM, So-Youn ; KIM, Jae-Woo ; KYUNG JIN ROH ; SEONG, Je-Kyung ; LEE, Nam Taek ; KANG-YELL CHOI ; KIM, Kyung-Sup ; AHNL, Yong-Ho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-b2cd95d274c2035fb752fae8bf0f660c185d915fefc5513afba19f977fdc3bd83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Line</topic><topic>Cell research</topic><topic>Chromans - pharmacology</topic><topic>Diabetes</topic><topic>Dimerization</topic><topic>DNA - metabolism</topic><topic>Enzyme Activation - drug effects</topic><topic>Evaluation</topic><topic>Gene expression</topic><topic>Gene Expression - drug effects</topic><topic>Glucokinase - genetics</topic><topic>Glucose</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Insulin</topic><topic>Islets of Langerhans - enzymology</topic><topic>Mice</topic><topic>Mutagenesis, Site-Directed</topic><topic>Peroxisomes</topic><topic>Physiological aspects</topic><topic>Plasmids</topic><topic>Promoter Regions, Genetic</topic><topic>Rats</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>Receptors, Cytoplasmic and Nuclear - physiology</topic><topic>Receptors, Retinoic Acid - metabolism</topic><topic>Response Elements</topic><topic>Retinoid X Receptors</topic><topic>Thiazoles - pharmacology</topic><topic>Thiazolidinediones</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription Factors - pharmacology</topic><topic>Transcription Factors - physiology</topic><topic>Transcriptional Activation</topic><topic>Transfection</topic><topic>Troglitazone</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>KIM, Ha-Il</creatorcontrib><creatorcontrib>CHA, Ji-Young</creatorcontrib><creatorcontrib>KIM, So-Youn</creatorcontrib><creatorcontrib>KIM, Jae-Woo</creatorcontrib><creatorcontrib>KYUNG JIN ROH</creatorcontrib><creatorcontrib>SEONG, Je-Kyung</creatorcontrib><creatorcontrib>LEE, Nam Taek</creatorcontrib><creatorcontrib>KANG-YELL CHOI</creatorcontrib><creatorcontrib>KIM, Kyung-Sup</creatorcontrib><creatorcontrib>AHNL, Yong-Ho</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>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Applied & Life Sciences</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>KIM, Ha-Il</au><au>CHA, Ji-Young</au><au>KIM, So-Youn</au><au>KIM, Jae-Woo</au><au>KYUNG JIN ROH</au><au>SEONG, Je-Kyung</au><au>LEE, Nam Taek</au><au>KANG-YELL CHOI</au><au>KIM, Kyung-Sup</au><au>AHNL, Yong-Ho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2002-03-01</date><risdate>2002</risdate><volume>51</volume><issue>3</issue><spage>676</spage><epage>685</epage><pages>676-685</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells
Ha-il Kim 1 ,
Ji-Young Cha 1 ,
So-Youn Kim 1 ,
Jae-woo Kim 1 ,
Kyung Jin Roh 2 ,
Je-Kyung Seong 2 ,
Nam Taek Lee 3 ,
Kang-Yell Choi 1 ,
Kyung-Sup Kim 1 and
Yong-ho Ahn 1
1 Department of Biochemistry and Molecular Biology, the Institute of Genetic Science, Yonsei University College of Medicine,
Seoul, Korea
2 Department of Laboratory Animal Medicine, Medical Research Center, Yonsei, College of Medicine, Seoul, Korea
3 Department of Chemistry, Korea Military Academy, Seoul, Korea
Abstract
Thiazolidinediones, synthetic ligands of peroxisomal proliferator-activated receptor-γ (PPAR-γ), improve peripheral insulin
sensitivity and glucose-stimulated insulin secretion in pancreatic β-cells. To explore the role of PPAR-γ in glucose sensing
of β-cells, we have dissected the β-cell-specific glucokinase (βGK) promoter, which constitutes glucose-sensing apparatus
in pancreatic β-cells, and identified a peroxisomal proliferator response element (PPRE) in the promoter. The βGK-PPRE is
located in the region between +47 and +68 bp. PPAR-γ/retinoid X receptor-α heterodimer binds to the element and activates
the βGK promoter. The βGK promoter lacking or having mutations in PPRE cannot be activated by PPAR-γ. PPAR-γ activates the
βGK promoter in β-cells as well as non-β-cells. Furthermore, troglitazone increases endogenous GK expression and its enzyme
activity in β-cell lines. These results indicate that PPAR-γ can regulate GK expression in β-cells. Taking these results together
with our previous work, we conclude that PPAR-γ regulates gene expression of glucose-sensing apparatus and thereby improves
glucose-sensing ability of β-cells, contributing to the restoration of β-cell function in type 2 diabetic subjects by troglitazone.
Footnotes
Address correspondence and reprint requests to Yong-ho Ahn, Department of Biochemistry and Molecular Biology, Yonsei University
College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. E-mail: yha111{at}yumc.yonsei.ac.kr .
Received for publication 6 September 2001 and accepted in revised form 26 November 2001.
H.-I.K. and J.-Y.C. contributed equally to this work.
βGK, β-cell-specific GK; DMEM, Dulbecco’s modified Eagle’s medium; EMSA, electrophoretic mobility shift assay; FBS, fetal
bovine serum; GK, glucokinase; GSIS, glucose-stimulated insulin secretion; LGK, rat liver-specific GK; MODY, maturity-onset
diabetes of the young; PDX-1, pancreatic duodenal homeobox gene-1; PPAR, peroxisomal proliferator-activated receptor; PPRE,
peroxisomal proliferator response element; RPA, RNase protection assay; RXR-α, retinoid X receptor-α; TZD, thiazolidinedione.
DIABETES</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>11872666</pmid><doi>10.2337/diabetes.51.3.676</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0012-1797 |
| ispartof | Diabetes (New York, N.Y.), 2002-03, Vol.51 (3), p.676-685 |
| issn | 0012-1797 1939-327X |
| language | eng |
| recordid | cdi_gale_infotracacademiconefile_A84209409 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Biological and medical sciences Cell Line Cell research Chromans - pharmacology Diabetes Dimerization DNA - metabolism Enzyme Activation - drug effects Evaluation Gene expression Gene Expression - drug effects Glucokinase - genetics Glucose Hypoglycemic Agents - pharmacology Insulin Islets of Langerhans - enzymology Mice Mutagenesis, Site-Directed Peroxisomes Physiological aspects Plasmids Promoter Regions, Genetic Rats Receptors, Cytoplasmic and Nuclear - metabolism Receptors, Cytoplasmic and Nuclear - physiology Receptors, Retinoic Acid - metabolism Response Elements Retinoid X Receptors Thiazoles - pharmacology Thiazolidinediones Transcription Factors - metabolism Transcription Factors - pharmacology Transcription Factors - physiology Transcriptional Activation Transfection Troglitazone |
| title | Peroxisomal Proliferator-Activated Receptor-γ Upregulates Glucokinase Gene Expression in β-Cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-19T04%3A14%3A57IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Peroxisomal%20Proliferator-Activated%20Receptor-%CE%B3%20Upregulates%20Glucokinase%20Gene%20Expression%20in%20%CE%B2-Cells&rft.jtitle=Diabetes%20(New%20York,%20N.Y.)&rft.au=KIM,%20Ha-Il&rft.date=2002-03-01&rft.volume=51&rft.issue=3&rft.spage=676&rft.epage=685&rft.pages=676-685&rft.issn=0012-1797&rft.eissn=1939-327X&rft.coden=DIAEAZ&rft_id=info:doi/10.2337/diabetes.51.3.676&rft_dat=%3Cgale_pubme%3EA84209409%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=216474926&rft_id=info:pmid/11872666&rft_galeid=A84209409&rfr_iscdi=true |