Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose
Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose Xia Li 1 , Yu-Hsiang Shu 1 , Anny H. Xiang 1 , Enrique Trigo 2 , Johanna Kuusisto 3 , Jaana Hartiala 1 , 4 , Amy J. Swift 5 , Miwa Kawakubo 1 , Heather M. Stringham 6 , Lori L. Bonnycastle 5 , Jean M. Law...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2009-12, Vol.58 (12), p.2946-2953 |
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| creator | XIA LI SHU, Yu-Hsiang LAWRENCE, Jean M LAAKSO, Markku ALLAYEE, Hooman BUCHANAN, Thomas A WATANABE, Richard M XIANG, Anny H TRIGO, Enrique KUUSISTO, Johanna HARTIALA, Jaana SWIFT, Amy J KAWAKUBO, Miwa STRINGHAM, Heather M BONNYCASTLE, Lori L |
| description | Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose
Xia Li 1 ,
Yu-Hsiang Shu 1 ,
Anny H. Xiang 1 ,
Enrique Trigo 2 ,
Johanna Kuusisto 3 ,
Jaana Hartiala 1 , 4 ,
Amy J. Swift 5 ,
Miwa Kawakubo 1 ,
Heather M. Stringham 6 ,
Lori L. Bonnycastle 5 ,
Jean M. Lawrence 7 ,
Markku Laakso 3 ,
Hooman Allayee 1 , 4 ,
Thomas A. Buchanan 2 , 8 and
Richard M. Watanabe 1 , 8
1 Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine, University of Southern California,
Los Angeles, California;
2 Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles,
California;
3 Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland;
4 Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California;
5 Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland;
6 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan;
7 Research and Evaluation, Kaiser Permanente of Southern California, Pasadena, California;
8 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
Corresponding author: Richard M. Watanabe, rwatanab{at}usc.edu .
X.L. and Y.-H.S. contributed equally to this study.
Abstract
OBJECTIVE Glucokinase ( GCK ) and glucose-6-phosphatase catalytic subunit 2 ( G6PC2 ) regulate the glucose-cycling step in pancreatic β-cells and may regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been independently associated with fasting glucose, but their interaction on glucose-insulin relationships
is not well characterized.
RESEARCH DESIGN AND METHODS We tested whether these variants are associated with diabetes-related quantitative traits in Mexican Americans from the BetaGene
Study and attempted to replicate our findings in Finnish men from the METabolic Syndrome in Men (METSIM) Study.
RESULTS rs1799884 was not associated with any quantitative trait (corrected P > 0.1), whereas rs560887 was significantly associated with the oral glucose tolerance test 30-min incremental insulin response
(30′ Δinsulin, corrected P = 0.021). We found no association between quantitative traits and the multiplicative interaction between rs1799884 and rs560887
( P > 0.26). However, the additive effect of these single nucleotide polymorp |
| doi_str_mv | 10.2337/db09-0228 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_734157082</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A214093333</galeid><sourcerecordid>A214093333</sourcerecordid><originalsourceid>FETCH-LOGICAL-c645t-70e952eeb7e713e28fc30bd411a2c286f50cbe68576cb0136c59d83db1d948343</originalsourceid><addsrcrecordid>eNp9km2L1DAQx4so3rr6wi8gRRER7JmHtkneCEu5q4cLJ_iA70KaTrs5usmZtKd-e1N3uXNlMfMiYeY3_0wmkyRPMTollLK3bYNEhgjh95IFFlRklLBv95MFQphkmAl2kjwK4QohVEZ7mJxgwXKMS7pI5KptzWhuID3rOtBjSF2X1mBhNDr9qrxRo3E2NTatqw-psm1alx8rkkbfhQ3TEAOfQHv4Q83hcxVGY_u0HibtAjxOHnRqCPBkvy-TL-dnn6v32fqyvqhW60yXeTFmDIEoCEDDgGEKhHeaoqaNRSqiCS-7AukGSl6wUjcI01IXouW0bXArck5zukze7XSvp2YLrQY7ejXIa2-2yv-SThl5GLFmI3t3IwnjiHMeBV7tBbz7PkEY5dYEDcOgLLgpSEZzXDDESSSf_0Neucnb-DpJcJkLxHERoRc7qFcDSGM7F2_Vs6RcEZwjQee1TLIjVB_bH0t0FjoT3Qf86RE-Wgtbo48mvD5IiMwIP8deTSFIXq__V8ye1W4YoAcZv6u6PKqtvQvBQ3fbbYzkPJdynks5z2Vkn_39PXfkfhAj8HIPqKDV0HlltQm3HCEE5YWYhd7suI3pNz-MB9ka1cAI4e5QcImJJCIv6W9fhPP3</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>216490815</pqid></control><display><type>article</type><title>Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>XIA LI ; SHU, Yu-Hsiang ; LAWRENCE, Jean M ; LAAKSO, Markku ; ALLAYEE, Hooman ; BUCHANAN, Thomas A ; WATANABE, Richard M ; XIANG, Anny H ; TRIGO, Enrique ; KUUSISTO, Johanna ; HARTIALA, Jaana ; SWIFT, Amy J ; KAWAKUBO, Miwa ; STRINGHAM, Heather M ; BONNYCASTLE, Lori L</creator><creatorcontrib>XIA LI ; SHU, Yu-Hsiang ; LAWRENCE, Jean M ; LAAKSO, Markku ; ALLAYEE, Hooman ; BUCHANAN, Thomas A ; WATANABE, Richard M ; XIANG, Anny H ; TRIGO, Enrique ; KUUSISTO, Johanna ; HARTIALA, Jaana ; SWIFT, Amy J ; KAWAKUBO, Miwa ; STRINGHAM, Heather M ; BONNYCASTLE, Lori L</creatorcontrib><description>Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose
Xia Li 1 ,
Yu-Hsiang Shu 1 ,
Anny H. Xiang 1 ,
Enrique Trigo 2 ,
Johanna Kuusisto 3 ,
Jaana Hartiala 1 , 4 ,
Amy J. Swift 5 ,
Miwa Kawakubo 1 ,
Heather M. Stringham 6 ,
Lori L. Bonnycastle 5 ,
Jean M. Lawrence 7 ,
Markku Laakso 3 ,
Hooman Allayee 1 , 4 ,
Thomas A. Buchanan 2 , 8 and
Richard M. Watanabe 1 , 8
1 Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine, University of Southern California,
Los Angeles, California;
2 Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles,
California;
3 Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland;
4 Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California;
5 Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland;
6 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan;
7 Research and Evaluation, Kaiser Permanente of Southern California, Pasadena, California;
8 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
Corresponding author: Richard M. Watanabe, rwatanab{at}usc.edu .
X.L. and Y.-H.S. contributed equally to this study.
Abstract
OBJECTIVE Glucokinase ( GCK ) and glucose-6-phosphatase catalytic subunit 2 ( G6PC2 ) regulate the glucose-cycling step in pancreatic β-cells and may regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been independently associated with fasting glucose, but their interaction on glucose-insulin relationships
is not well characterized.
RESEARCH DESIGN AND METHODS We tested whether these variants are associated with diabetes-related quantitative traits in Mexican Americans from the BetaGene
Study and attempted to replicate our findings in Finnish men from the METabolic Syndrome in Men (METSIM) Study.
RESULTS rs1799884 was not associated with any quantitative trait (corrected P > 0.1), whereas rs560887 was significantly associated with the oral glucose tolerance test 30-min incremental insulin response
(30′ Δinsulin, corrected P = 0.021). We found no association between quantitative traits and the multiplicative interaction between rs1799884 and rs560887
( P > 0.26). However, the additive effect of these single nucleotide polymorphisms was associated with fasting glucose (corrected
P = 0.03) and 30′ Δinsulin (corrected P = 0.027). This additive association was replicated in METSIM (fasting glucose, P = 3.5 × 10 −10 30′ Δinsulin, P = 0.028). When we examined the relationship between fasting glucose and 30′ Δinsulin stratified by GCK and G6PC2 , we noted divergent changes in these quantitative traits for GCK but parallel changes for G6PC2 . We observed a similar pattern in METSIM.
CONCLUSIONS Our data suggest that variation in GCK and G6PC2 have additive effects on both fasting glucose and insulin secretion.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received February 18, 2009.
Accepted August 27, 2009.
© 2009 American Diabetes Association</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db09-0228</identifier><identifier>PMID: 19741163</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adult ; Aged ; Biological and medical sciences ; Blood glucose ; Blood Glucose - metabolism ; Blood sugar ; Body composition ; Care and treatment ; Control ; Diabetes ; Diabetes. Impaired glucose tolerance ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Families & family life ; Fasting ; Female ; Genetic aspects ; Genetic Variation ; Glucose ; Glucose-6-Phosphatase - genetics ; Hispanic Americans ; Humans ; Insulin ; Insulin - blood ; Insulin - metabolism ; Insulin Secretion ; Insulin-Secreting Cells - metabolism ; Male ; Measurement ; Medical sciences ; Metabolic syndrome ; Mexican Americans - genetics ; Middle Aged ; Original ; Pancreatic beta cells ; Phosphatase ; Physiological aspects ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases - genetics ; Type 2 diabetes</subject><ispartof>Diabetes (New York, N.Y.), 2009-12, Vol.58 (12), p.2946-2953</ispartof><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2009 American Diabetes Association</rights><rights>Copyright American Diabetes Association Dec 2009</rights><rights>2009 American Diabetes Association</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c645t-70e952eeb7e713e28fc30bd411a2c286f50cbe68576cb0136c59d83db1d948343</citedby><cites>FETCH-LOGICAL-c645t-70e952eeb7e713e28fc30bd411a2c286f50cbe68576cb0136c59d83db1d948343</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780888/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2780888/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22204598$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19741163$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>XIA LI</creatorcontrib><creatorcontrib>SHU, Yu-Hsiang</creatorcontrib><creatorcontrib>LAWRENCE, Jean M</creatorcontrib><creatorcontrib>LAAKSO, Markku</creatorcontrib><creatorcontrib>ALLAYEE, Hooman</creatorcontrib><creatorcontrib>BUCHANAN, Thomas A</creatorcontrib><creatorcontrib>WATANABE, Richard M</creatorcontrib><creatorcontrib>XIANG, Anny H</creatorcontrib><creatorcontrib>TRIGO, Enrique</creatorcontrib><creatorcontrib>KUUSISTO, Johanna</creatorcontrib><creatorcontrib>HARTIALA, Jaana</creatorcontrib><creatorcontrib>SWIFT, Amy J</creatorcontrib><creatorcontrib>KAWAKUBO, Miwa</creatorcontrib><creatorcontrib>STRINGHAM, Heather M</creatorcontrib><creatorcontrib>BONNYCASTLE, Lori L</creatorcontrib><title>Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose
Xia Li 1 ,
Yu-Hsiang Shu 1 ,
Anny H. Xiang 1 ,
Enrique Trigo 2 ,
Johanna Kuusisto 3 ,
Jaana Hartiala 1 , 4 ,
Amy J. Swift 5 ,
Miwa Kawakubo 1 ,
Heather M. Stringham 6 ,
Lori L. Bonnycastle 5 ,
Jean M. Lawrence 7 ,
Markku Laakso 3 ,
Hooman Allayee 1 , 4 ,
Thomas A. Buchanan 2 , 8 and
Richard M. Watanabe 1 , 8
1 Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine, University of Southern California,
Los Angeles, California;
2 Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles,
California;
3 Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland;
4 Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California;
5 Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland;
6 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan;
7 Research and Evaluation, Kaiser Permanente of Southern California, Pasadena, California;
8 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
Corresponding author: Richard M. Watanabe, rwatanab{at}usc.edu .
X.L. and Y.-H.S. contributed equally to this study.
Abstract
OBJECTIVE Glucokinase ( GCK ) and glucose-6-phosphatase catalytic subunit 2 ( G6PC2 ) regulate the glucose-cycling step in pancreatic β-cells and may regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been independently associated with fasting glucose, but their interaction on glucose-insulin relationships
is not well characterized.
RESEARCH DESIGN AND METHODS We tested whether these variants are associated with diabetes-related quantitative traits in Mexican Americans from the BetaGene
Study and attempted to replicate our findings in Finnish men from the METabolic Syndrome in Men (METSIM) Study.
RESULTS rs1799884 was not associated with any quantitative trait (corrected P > 0.1), whereas rs560887 was significantly associated with the oral glucose tolerance test 30-min incremental insulin response
(30′ Δinsulin, corrected P = 0.021). We found no association between quantitative traits and the multiplicative interaction between rs1799884 and rs560887
( P > 0.26). However, the additive effect of these single nucleotide polymorphisms was associated with fasting glucose (corrected
P = 0.03) and 30′ Δinsulin (corrected P = 0.027). This additive association was replicated in METSIM (fasting glucose, P = 3.5 × 10 −10 30′ Δinsulin, P = 0.028). When we examined the relationship between fasting glucose and 30′ Δinsulin stratified by GCK and G6PC2 , we noted divergent changes in these quantitative traits for GCK but parallel changes for G6PC2 . We observed a similar pattern in METSIM.
CONCLUSIONS Our data suggest that variation in GCK and G6PC2 have additive effects on both fasting glucose and insulin secretion.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received February 18, 2009.
Accepted August 27, 2009.
© 2009 American Diabetes Association</description><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Blood glucose</subject><subject>Blood Glucose - metabolism</subject><subject>Blood sugar</subject><subject>Body composition</subject><subject>Care and treatment</subject><subject>Control</subject><subject>Diabetes</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Families & family life</subject><subject>Fasting</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic Variation</subject><subject>Glucose</subject><subject>Glucose-6-Phosphatase - genetics</subject><subject>Hispanic Americans</subject><subject>Humans</subject><subject>Insulin</subject><subject>Insulin - blood</subject><subject>Insulin - metabolism</subject><subject>Insulin Secretion</subject><subject>Insulin-Secreting Cells - metabolism</subject><subject>Male</subject><subject>Measurement</subject><subject>Medical sciences</subject><subject>Metabolic syndrome</subject><subject>Mexican Americans - genetics</subject><subject>Middle Aged</subject><subject>Original</subject><subject>Pancreatic beta cells</subject><subject>Phosphatase</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Type 2 diabetes</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9km2L1DAQx4so3rr6wi8gRRER7JmHtkneCEu5q4cLJ_iA70KaTrs5usmZtKd-e1N3uXNlMfMiYeY3_0wmkyRPMTollLK3bYNEhgjh95IFFlRklLBv95MFQphkmAl2kjwK4QohVEZ7mJxgwXKMS7pI5KptzWhuID3rOtBjSF2X1mBhNDr9qrxRo3E2NTatqw-psm1alx8rkkbfhQ3TEAOfQHv4Q83hcxVGY_u0HibtAjxOHnRqCPBkvy-TL-dnn6v32fqyvqhW60yXeTFmDIEoCEDDgGEKhHeaoqaNRSqiCS-7AukGSl6wUjcI01IXouW0bXArck5zukze7XSvp2YLrQY7ejXIa2-2yv-SThl5GLFmI3t3IwnjiHMeBV7tBbz7PkEY5dYEDcOgLLgpSEZzXDDESSSf_0Neucnb-DpJcJkLxHERoRc7qFcDSGM7F2_Vs6RcEZwjQee1TLIjVB_bH0t0FjoT3Qf86RE-Wgtbo48mvD5IiMwIP8deTSFIXq__V8ye1W4YoAcZv6u6PKqtvQvBQ3fbbYzkPJdynks5z2Vkn_39PXfkfhAj8HIPqKDV0HlltQm3HCEE5YWYhd7suI3pNz-MB9ka1cAI4e5QcImJJCIv6W9fhPP3</recordid><startdate>20091201</startdate><enddate>20091201</enddate><creator>XIA LI</creator><creator>SHU, Yu-Hsiang</creator><creator>LAWRENCE, Jean M</creator><creator>LAAKSO, Markku</creator><creator>ALLAYEE, Hooman</creator><creator>BUCHANAN, Thomas A</creator><creator>WATANABE, Richard M</creator><creator>XIANG, Anny H</creator><creator>TRIGO, Enrique</creator><creator>KUUSISTO, Johanna</creator><creator>HARTIALA, Jaana</creator><creator>SWIFT, Amy J</creator><creator>KAWAKUBO, Miwa</creator><creator>STRINGHAM, Heather M</creator><creator>BONNYCASTLE, Lori L</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>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20091201</creationdate><title>Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose</title><author>XIA LI ; SHU, Yu-Hsiang ; LAWRENCE, Jean M ; LAAKSO, Markku ; ALLAYEE, Hooman ; BUCHANAN, Thomas A ; WATANABE, Richard M ; XIANG, Anny H ; TRIGO, Enrique ; KUUSISTO, Johanna ; HARTIALA, Jaana ; SWIFT, Amy J ; KAWAKUBO, Miwa ; STRINGHAM, Heather M ; BONNYCASTLE, Lori L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c645t-70e952eeb7e713e28fc30bd411a2c286f50cbe68576cb0136c59d83db1d948343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Blood glucose</topic><topic>Blood Glucose - metabolism</topic><topic>Blood sugar</topic><topic>Body composition</topic><topic>Care and treatment</topic><topic>Control</topic><topic>Diabetes</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Families & family life</topic><topic>Fasting</topic><topic>Female</topic><topic>Genetic aspects</topic><topic>Genetic Variation</topic><topic>Glucose</topic><topic>Glucose-6-Phosphatase - genetics</topic><topic>Hispanic Americans</topic><topic>Humans</topic><topic>Insulin</topic><topic>Insulin - blood</topic><topic>Insulin - metabolism</topic><topic>Insulin Secretion</topic><topic>Insulin-Secreting Cells - metabolism</topic><topic>Male</topic><topic>Measurement</topic><topic>Medical sciences</topic><topic>Metabolic syndrome</topic><topic>Mexican Americans - genetics</topic><topic>Middle Aged</topic><topic>Original</topic><topic>Pancreatic beta cells</topic><topic>Phosphatase</topic><topic>Physiological aspects</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Protein-Serine-Threonine Kinases - genetics</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>XIA LI</creatorcontrib><creatorcontrib>SHU, Yu-Hsiang</creatorcontrib><creatorcontrib>LAWRENCE, Jean M</creatorcontrib><creatorcontrib>LAAKSO, Markku</creatorcontrib><creatorcontrib>ALLAYEE, Hooman</creatorcontrib><creatorcontrib>BUCHANAN, Thomas A</creatorcontrib><creatorcontrib>WATANABE, Richard M</creatorcontrib><creatorcontrib>XIANG, Anny H</creatorcontrib><creatorcontrib>TRIGO, Enrique</creatorcontrib><creatorcontrib>KUUSISTO, Johanna</creatorcontrib><creatorcontrib>HARTIALA, Jaana</creatorcontrib><creatorcontrib>SWIFT, Amy J</creatorcontrib><creatorcontrib>KAWAKUBO, Miwa</creatorcontrib><creatorcontrib>STRINGHAM, Heather M</creatorcontrib><creatorcontrib>BONNYCASTLE, Lori L</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 One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>XIA LI</au><au>SHU, Yu-Hsiang</au><au>LAWRENCE, Jean M</au><au>LAAKSO, Markku</au><au>ALLAYEE, Hooman</au><au>BUCHANAN, Thomas A</au><au>WATANABE, Richard M</au><au>XIANG, Anny H</au><au>TRIGO, Enrique</au><au>KUUSISTO, Johanna</au><au>HARTIALA, Jaana</au><au>SWIFT, Amy J</au><au>KAWAKUBO, Miwa</au><au>STRINGHAM, Heather M</au><au>BONNYCASTLE, Lori L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2009-12-01</date><risdate>2009</risdate><volume>58</volume><issue>12</issue><spage>2946</spage><epage>2953</epage><pages>2946-2953</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose
Xia Li 1 ,
Yu-Hsiang Shu 1 ,
Anny H. Xiang 1 ,
Enrique Trigo 2 ,
Johanna Kuusisto 3 ,
Jaana Hartiala 1 , 4 ,
Amy J. Swift 5 ,
Miwa Kawakubo 1 ,
Heather M. Stringham 6 ,
Lori L. Bonnycastle 5 ,
Jean M. Lawrence 7 ,
Markku Laakso 3 ,
Hooman Allayee 1 , 4 ,
Thomas A. Buchanan 2 , 8 and
Richard M. Watanabe 1 , 8
1 Department of Preventive Medicine, Division of Biostatistics, Keck School of Medicine, University of Southern California,
Los Angeles, California;
2 Department of Medicine, Division of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles,
California;
3 Department of Medicine, University of Kuopio and Kuopio University Hospital, Kuopio, Finland;
4 Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California;
5 Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland;
6 Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan;
7 Research and Evaluation, Kaiser Permanente of Southern California, Pasadena, California;
8 Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California.
Corresponding author: Richard M. Watanabe, rwatanab{at}usc.edu .
X.L. and Y.-H.S. contributed equally to this study.
Abstract
OBJECTIVE Glucokinase ( GCK ) and glucose-6-phosphatase catalytic subunit 2 ( G6PC2 ) regulate the glucose-cycling step in pancreatic β-cells and may regulate insulin secretion. GCK rs1799884 and G6PC2 rs560887 have been independently associated with fasting glucose, but their interaction on glucose-insulin relationships
is not well characterized.
RESEARCH DESIGN AND METHODS We tested whether these variants are associated with diabetes-related quantitative traits in Mexican Americans from the BetaGene
Study and attempted to replicate our findings in Finnish men from the METabolic Syndrome in Men (METSIM) Study.
RESULTS rs1799884 was not associated with any quantitative trait (corrected P > 0.1), whereas rs560887 was significantly associated with the oral glucose tolerance test 30-min incremental insulin response
(30′ Δinsulin, corrected P = 0.021). We found no association between quantitative traits and the multiplicative interaction between rs1799884 and rs560887
( P > 0.26). However, the additive effect of these single nucleotide polymorphisms was associated with fasting glucose (corrected
P = 0.03) and 30′ Δinsulin (corrected P = 0.027). This additive association was replicated in METSIM (fasting glucose, P = 3.5 × 10 −10 30′ Δinsulin, P = 0.028). When we examined the relationship between fasting glucose and 30′ Δinsulin stratified by GCK and G6PC2 , we noted divergent changes in these quantitative traits for GCK but parallel changes for G6PC2 . We observed a similar pattern in METSIM.
CONCLUSIONS Our data suggest that variation in GCK and G6PC2 have additive effects on both fasting glucose and insulin secretion.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received February 18, 2009.
Accepted August 27, 2009.
© 2009 American Diabetes Association</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>19741163</pmid><doi>10.2337/db09-0228</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Adult Aged Biological and medical sciences Blood glucose Blood Glucose - metabolism Blood sugar Body composition Care and treatment Control Diabetes Diabetes. Impaired glucose tolerance Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Families & family life Fasting Female Genetic aspects Genetic Variation Glucose Glucose-6-Phosphatase - genetics Hispanic Americans Humans Insulin Insulin - blood Insulin - metabolism Insulin Secretion Insulin-Secreting Cells - metabolism Male Measurement Medical sciences Metabolic syndrome Mexican Americans - genetics Middle Aged Original Pancreatic beta cells Phosphatase Physiological aspects Polymorphism, Single Nucleotide Protein-Serine-Threonine Kinases - genetics Type 2 diabetes |
| title | Additive Effects of Genetic Variation in GCK and G6PC2 on Insulin Secretion and Fasting Glucose |
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