GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response
Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3) plays...
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| description | Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3) plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM). Thus, the aims of this study were (i) to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii) to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS) or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT) women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators. |
| doi_str_mv | 10.1371/journal.pone.0115854 |
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Recent studies have shown that glycogen synthase kinase 3 (GSK3) plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM). Thus, the aims of this study were (i) to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii) to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS) or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT) women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0115854</identifier><identifier>PMID: 25541965</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adhesion ; Adipose tissue ; Adipose Tissue - drug effects ; Adipose Tissue - metabolism ; Adult ; Bacteria ; Biology and Life Sciences ; Body fat ; Body mass ; Chemokines ; Chemokines - metabolism ; Cytokines ; Diabetes mellitus ; Diabetes, Gestational - enzymology ; Diabetes, Gestational - metabolism ; Endotoxins ; Explants ; Female ; Gene expression ; Gene Expression Regulation, Enzymologic - drug effects ; Gestational diabetes ; Glucose ; Glycogen ; Glycogen synthase kinase 3 ; Glycogen Synthase Kinase 3 - antagonists & inhibitors ; Glycogen Synthase Kinase 3 - metabolism ; Glycogen Synthase Kinase 3 beta ; Gsk3 protein ; Humans ; Infections ; Inflammation ; Inflammation - chemically induced ; Inflammation - enzymology ; Inflammation - metabolism ; Inflammatory response ; Inhibitors ; Insulin ; Insulin resistance ; Intercellular adhesion molecule 1 ; Intercellular Adhesion Molecule-1 - genetics ; Interleukin 6 ; Interleukin 8 ; Interleukin-1beta - pharmacology ; Kinases ; Lipopolysaccharides ; Lipopolysaccharides - pharmacology ; Medicine and Health Sciences ; Monocyte chemoattractant protein 1 ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - metabolism ; Muscles ; Obesity - complications ; Pregnancy ; Pyridines - pharmacology ; Pyrimidines - pharmacology ; Rodents ; Serine ; Skeletal muscle ; Tissues ; Tumor necrosis factor-α ; Vascular cell adhesion molecule 1 ; Vascular Cell Adhesion Molecule-1 - genetics ; Western blotting ; Womens health</subject><ispartof>PloS one, 2014-12, Vol.9 (12), p.e115854-e115854</ispartof><rights>2014 Martha Lappas. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Martha Lappas 2014 Martha Lappas</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-d74fc5f8d07999ca9da51948019782b72072c468f8a2de70a5ff5a430d2c9dec3</citedby><cites>FETCH-LOGICAL-c526t-d74fc5f8d07999ca9da51948019782b72072c468f8a2de70a5ff5a430d2c9dec3</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/PMC4277409/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277409/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25541965$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Sanchez-Margalet, Victor</contributor><creatorcontrib>Lappas, Martha</creatorcontrib><title>GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3) plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM). Thus, the aims of this study were (i) to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii) to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS) or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT) women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. 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antagonists & inhibitors</subject><subject>Glycogen Synthase Kinase 3 - metabolism</subject><subject>Glycogen Synthase Kinase 3 beta</subject><subject>Gsk3 protein</subject><subject>Humans</subject><subject>Infections</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - enzymology</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory response</subject><subject>Inhibitors</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Intercellular adhesion molecule 1</subject><subject>Intercellular Adhesion Molecule-1 - genetics</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Interleukin-1beta - pharmacology</subject><subject>Kinases</subject><subject>Lipopolysaccharides</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Medicine and Health Sciences</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Muscles</subject><subject>Obesity - complications</subject><subject>Pregnancy</subject><subject>Pyridines - pharmacology</subject><subject>Pyrimidines - pharmacology</subject><subject>Rodents</subject><subject>Serine</subject><subject>Skeletal muscle</subject><subject>Tissues</subject><subject>Tumor necrosis factor-α</subject><subject>Vascular cell adhesion molecule 1</subject><subject>Vascular Cell Adhesion Molecule-1 - genetics</subject><subject>Western blotting</subject><subject>Womens health</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</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><sourceid>DOA</sourceid><recordid>eNptUsFuEzEQXSEQLYU_QGCJC5cEe22v1xckVEGpqMQBOFsTezZx2F0H20vUb-jf9EP4JpwmrVrEyaOZN8_vjV5VvWR0zrhi79ZhiiP0800YcU4Zk60Uj6pjpnk9a2rKH9-rj6pnKa0plbxtmqfVUS2lYLqRx9XV2bcv_M818Yn40UaEhK5UBJzfhIQk-5QmJDA6kn5ijxl6MkzJ9ki6GAayDQOOZOvziiwxZcg-FFHEeVhgxkS2K4xIfCYRl1MPu1ZelcbY9TAMkEO8LKNUTCR8Xj3poE_44vCeVD8-ffx--nl28fXs_PTDxczKuskzp0RnZdc6qrTWFrQDybRoKdOqrReqpqq2omm7FmqHioLsOgmCU1db7dDyk-r1nnfTh2QOd0yGNYJKqbWQBXG-R7gAa7OJfoB4aQJ4c9MIcWkgZl-uYISWmkNLG-hq0SLTiBa5VI4zxzhXhev94bdpMaCzOOYI_QPSh5PRr8wy_DaiVkpQXQjeHghi-DWVI5vBJ4t9DyOG6UY3o6xRfKf7zT_Q_7sTe5SNIaWI3Z0YRs0uW7dbZpctc8hWWXt138jd0m2Y-F9dr9Bg</recordid><startdate>20141226</startdate><enddate>20141226</enddate><creator>Lappas, Martha</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20141226</creationdate><title>GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response</title><author>Lappas, Martha</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-d74fc5f8d07999ca9da51948019782b72072c468f8a2de70a5ff5a430d2c9dec3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adhesion</topic><topic>Adipose tissue</topic><topic>Adipose Tissue - drug effects</topic><topic>Adipose Tissue - metabolism</topic><topic>Adult</topic><topic>Bacteria</topic><topic>Biology and Life Sciences</topic><topic>Body fat</topic><topic>Body mass</topic><topic>Chemokines</topic><topic>Chemokines - metabolism</topic><topic>Cytokines</topic><topic>Diabetes mellitus</topic><topic>Diabetes, Gestational - enzymology</topic><topic>Diabetes, Gestational - metabolism</topic><topic>Endotoxins</topic><topic>Explants</topic><topic>Female</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Enzymologic - drug effects</topic><topic>Gestational diabetes</topic><topic>Glucose</topic><topic>Glycogen</topic><topic>Glycogen synthase kinase 3</topic><topic>Glycogen Synthase Kinase 3 - antagonists & inhibitors</topic><topic>Glycogen Synthase Kinase 3 - metabolism</topic><topic>Glycogen Synthase Kinase 3 beta</topic><topic>Gsk3 protein</topic><topic>Humans</topic><topic>Infections</topic><topic>Inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - enzymology</topic><topic>Inflammation - metabolism</topic><topic>Inflammatory response</topic><topic>Inhibitors</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Intercellular adhesion molecule 1</topic><topic>Intercellular Adhesion Molecule-1 - genetics</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Interleukin-1beta - pharmacology</topic><topic>Kinases</topic><topic>Lipopolysaccharides</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Medicine and Health Sciences</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Muscles</topic><topic>Obesity - complications</topic><topic>Pregnancy</topic><topic>Pyridines - pharmacology</topic><topic>Pyrimidines - pharmacology</topic><topic>Rodents</topic><topic>Serine</topic><topic>Skeletal muscle</topic><topic>Tissues</topic><topic>Tumor necrosis factor-α</topic><topic>Vascular cell adhesion molecule 1</topic><topic>Vascular Cell Adhesion Molecule-1 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lappas, Martha</au><au>Sanchez-Margalet, Victor</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-12-26</date><risdate>2014</risdate><volume>9</volume><issue>12</issue><spage>e115854</spage><epage>e115854</epage><pages>e115854-e115854</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Infection and inflammation, through their ability to increase pro-inflammatory cytokines and chemokines and adhesion molecules, are thought to play a central role in the pathophysiology of insulin resistance and type 2 diabetes. Recent studies have shown that glycogen synthase kinase 3 (GSK3) plays a central role in regulating this inflammation. There are, however, no studies on the role of GSK3 in pregnancies complicated by gestational diabetes mellitus (GDM). Thus, the aims of this study were (i) to determine whether GSK3 is increased in adipose tissue and skeletal muscle from women with GDM; and (ii) to investigate the effect of GSK3 inhibition on inflammation in the presence of inflammation induced by bacterial endotoxin lipopolysaccharide (LPS) or the pro-inflammatory cytokine IL-1β. Human omental adipose tissue and skeletal muscle were obtained from normal glucose tolerant (NGT) women and BMI-matched women with diet-control GDM at the time of Caesarean section. Western blotting was performed to determine GSK3 protein expression. Tissue explants were performed to determine the effect of the GSK3 inhibitor CHIR99021 on markers of inflammation. When compared to women with NGT, omental adipose tissue and skeletal muscle obtained from women with diet-controlled GDM had significantly higher GSK3β activity as evidenced by a decrease in the expression of GSK3β phosphorylated at serine 9. The GSK3 inhibitor CHIR99021 significantly reduced the gene expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β and IL-6; the pro-inflammatory chemokines IL-8 and MCP-1; and the adhesion molecules ICAM-1 and VCAM-1 in tissues stimulated with LPS or IL-1β. In conclusion, GSK3 activity is increased in GDM adipose tissue and skeletal muscle and regulates infection- and inflammation-induced pro-inflammatory mediators.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25541965</pmid><doi>10.1371/journal.pone.0115854</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Adhesion Adipose tissue Adipose Tissue - drug effects Adipose Tissue - metabolism Adult Bacteria Biology and Life Sciences Body fat Body mass Chemokines Chemokines - metabolism Cytokines Diabetes mellitus Diabetes, Gestational - enzymology Diabetes, Gestational - metabolism Endotoxins Explants Female Gene expression Gene Expression Regulation, Enzymologic - drug effects Gestational diabetes Glucose Glycogen Glycogen synthase kinase 3 Glycogen Synthase Kinase 3 - antagonists & inhibitors Glycogen Synthase Kinase 3 - metabolism Glycogen Synthase Kinase 3 beta Gsk3 protein Humans Infections Inflammation Inflammation - chemically induced Inflammation - enzymology Inflammation - metabolism Inflammatory response Inhibitors Insulin Insulin resistance Intercellular adhesion molecule 1 Intercellular Adhesion Molecule-1 - genetics Interleukin 6 Interleukin 8 Interleukin-1beta - pharmacology Kinases Lipopolysaccharides Lipopolysaccharides - pharmacology Medicine and Health Sciences Monocyte chemoattractant protein 1 Muscle, Skeletal - drug effects Muscle, Skeletal - metabolism Muscles Obesity - complications Pregnancy Pyridines - pharmacology Pyrimidines - pharmacology Rodents Serine Skeletal muscle Tissues Tumor necrosis factor-α Vascular cell adhesion molecule 1 Vascular Cell Adhesion Molecule-1 - genetics Western blotting Womens health |
| title | GSK3β is increased in adipose tissue and skeletal muscle from women with gestational diabetes where it regulates the inflammatory response |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-22T02%3A44%3A51IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=GSK3%CE%B2%20is%20increased%20in%20adipose%20tissue%20and%20skeletal%20muscle%20from%20women%20with%20gestational%20diabetes%20where%20it%20regulates%20the%20inflammatory%20response&rft.jtitle=PloS%20one&rft.au=Lappas,%20Martha&rft.date=2014-12-26&rft.volume=9&rft.issue=12&rft.spage=e115854&rft.epage=e115854&rft.pages=e115854-e115854&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0115854&rft_dat=%3Cproquest_plos_%3E3537400891%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1640559945&rft_id=info:pmid/25541965&rft_doaj_id=oai_doaj_org_article_49593a806af248e19eece357d31d1337&rfr_iscdi=true |