Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes
Ursolic acid (UA), a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels. The objective of the present study was to determine the e...
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| creator | He, Yonghan Li, Wen Li, Ying Zhang, Shuocheng Wang, Yanwen Sun, Changhao |
| description | Ursolic acid (UA), a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels.
The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes.
The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively). 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI) 3-kinase (PI3K) inhibitor wortmannin (1 µM), but not by SB203580 (10 µM), the inhibitor of mitogen-activated protein kinase (MAPK), or compound C (2.5 µM), the inhibitor of AMP-activated kinase (AMPK) inhibitor. Furthermore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK) and phosphoinositide-dependent serine/threoninekinase (AKT) were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC) and the expression of glucose transporter 4 (GLUT4) were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied.
Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect. |
| doi_str_mv | 10.1371/journal.pone.0110711 |
| format | Article |
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The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes.
The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively). 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI) 3-kinase (PI3K) inhibitor wortmannin (1 µM), but not by SB203580 (10 µM), the inhibitor of mitogen-activated protein kinase (MAPK), or compound C (2.5 µM), the inhibitor of AMP-activated kinase (AMPK) inhibitor. Furthermore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK) and phosphoinositide-dependent serine/threoninekinase (AKT) were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC) and the expression of glucose transporter 4 (GLUT4) were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied.
Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0110711</identifier><identifier>PMID: 25329874</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; 3T3-L1 Cells ; Acids ; Adipocytes ; Adipocytes - cytology ; Adipocytes - metabolism ; Adipose tissue ; AKT protein ; AMP ; Animals ; Anti-Infective Agents - pharmacology ; Biology and Life Sciences ; Cell Membrane - metabolism ; Councils ; Crop diseases ; Cytoplasm ; Cytoplasm - metabolism ; Diabetes ; Diabetes mellitus ; Enzyme inhibitors ; Fluorescence ; Glucose ; Glucose - metabolism ; Glucose transport ; Glucose transporter ; Glucose Transporter Type 4 - metabolism ; Homeostasis ; Hygiene ; Inhibitors ; Insulin ; Insulin resistance ; Kinases ; Laboratories ; Life sciences ; Liver diseases ; MAP kinase ; Medicine and Health Sciences ; Metabolism ; Mice ; Nutrition research ; Phosphatidylinositol 3-Kinases - metabolism ; Preadipocytes ; Protein kinase C ; Protein Kinase Inhibitors - pharmacology ; Protein Transport - drug effects ; Proteins ; Public health ; Rodents ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Tissues ; Translocation ; Triterpenes - pharmacology ; Ursolic Acid ; Western blotting ; Wortmannin</subject><ispartof>PloS one, 2014-10, Vol.9 (10), p.e110711-e110711</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 He et al. 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 He et al 2014 He et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-c5588715e17e26432788958af5c9584c5a506304149d6e3d2736ccb4f9e6d7a93</citedby><cites>FETCH-LOGICAL-c692t-c5588715e17e26432788958af5c9584c5a506304149d6e3d2736ccb4f9e6d7a93</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/PMC4203820/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4203820/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2100,2926,23864,27922,27923,53789,53791,79370,79371</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25329874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Tang, Chih-Hsin</contributor><creatorcontrib>He, Yonghan</creatorcontrib><creatorcontrib>Li, Wen</creatorcontrib><creatorcontrib>Li, Ying</creatorcontrib><creatorcontrib>Zhang, Shuocheng</creatorcontrib><creatorcontrib>Wang, Yanwen</creatorcontrib><creatorcontrib>Sun, Changhao</creatorcontrib><title>Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ursolic acid (UA), a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels.
The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes.
The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively). 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI) 3-kinase (PI3K) inhibitor wortmannin (1 µM), but not by SB203580 (10 µM), the inhibitor of mitogen-activated protein kinase (MAPK), or compound C (2.5 µM), the inhibitor of AMP-activated kinase (AMPK) inhibitor. Furthermore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK) and phosphoinositide-dependent serine/threoninekinase (AKT) were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC) and the expression of glucose transporter 4 (GLUT4) were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied.
Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>3T3-L1 Cells</subject><subject>Acids</subject><subject>Adipocytes</subject><subject>Adipocytes - cytology</subject><subject>Adipocytes - metabolism</subject><subject>Adipose tissue</subject><subject>AKT protein</subject><subject>AMP</subject><subject>Animals</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Biology and Life Sciences</subject><subject>Cell Membrane - metabolism</subject><subject>Councils</subject><subject>Crop diseases</subject><subject>Cytoplasm</subject><subject>Cytoplasm - metabolism</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Enzyme inhibitors</subject><subject>Fluorescence</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucose transport</subject><subject>Glucose transporter</subject><subject>Glucose Transporter Type 4 - metabolism</subject><subject>Homeostasis</subject><subject>Hygiene</subject><subject>Inhibitors</subject><subject>Insulin</subject><subject>Insulin resistance</subject><subject>Kinases</subject><subject>Laboratories</subject><subject>Life sciences</subject><subject>Liver diseases</subject><subject>MAP kinase</subject><subject>Medicine and Health Sciences</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Nutrition research</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Preadipocytes</subject><subject>Protein kinase C</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein Transport - drug effects</subject><subject>Proteins</subject><subject>Public health</subject><subject>Rodents</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Tissues</subject><subject>Translocation</subject><subject>Triterpenes - pharmacology</subject><subject>Ursolic Acid</subject><subject>Western blotting</subject><subject>Wortmannin</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>eNqNkl2L1DAUhoso7jr6D0QLgujFjPlq0t4Iy-LH4MKKunsbMulpm7XTdJNUnX9vutNdprIXEsIJyfOek5y8SfIcoxWmAr-7soPrVLvqbQcrhDESGD9IjnFByZITRB8erI-SJ95fIZTRnPPHyRHJKClywY6TywvnbWt0qrQpU9NpB8qDT-t20NZDOvRB_YQ0NM4OdRMjpF_X9EvqTR2Lm65OexWa32oXtakqTW_1LoB_mjyqVOvh2RQXycXHDz9OPy_Pzj-tT0_OlpoXJCx1luW5wBlgAYQzSkSeF1muqkzHwHSmMsQpYpgVJQdaEkG51htWFcBLoQq6SF7u8_at9XJqiZeYY0ZFwRGJxHpPlFZdyd6ZrXI7aZWRNxvW1VK5YHQLEquNIDGv4JQwpOlGq2xDgBWCIITYWO39VG3YbKHU0AWn2lnS-UlnGlnbX5LFP8jjXCRvpgTOXg_gg9war6FtVQd2uLl3RsY53vvVP-j9r5uoWsUHmK6ysa4ek8oThnNMC4pxpFb3UHGUsDU6-qcycX8meDsTRCbAn1CrwXu5_v7t_9nzyzn7-oBtQLWhifYbgrGdn4NsD2pnvXdQ3TUZIzna_7YbcrS_nOwfZS8OP-hOdOt3-hdhOf01</recordid><startdate>20141020</startdate><enddate>20141020</enddate><creator>He, Yonghan</creator><creator>Li, Wen</creator><creator>Li, Ying</creator><creator>Zhang, Shuocheng</creator><creator>Wang, Yanwen</creator><creator>Sun, Changhao</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>IOV</scope><scope>ISR</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>AEUYN</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>20141020</creationdate><title>Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes</title><author>He, Yonghan ; Li, Wen ; Li, Ying ; Zhang, Shuocheng ; Wang, Yanwen ; Sun, Changhao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-c5588715e17e26432788958af5c9584c5a506304149d6e3d2736ccb4f9e6d7a93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>3T3-L1 Cells</topic><topic>Acids</topic><topic>Adipocytes</topic><topic>Adipocytes - cytology</topic><topic>Adipocytes - metabolism</topic><topic>Adipose tissue</topic><topic>AKT protein</topic><topic>AMP</topic><topic>Animals</topic><topic>Anti-Infective Agents - pharmacology</topic><topic>Biology and Life Sciences</topic><topic>Cell Membrane - metabolism</topic><topic>Councils</topic><topic>Crop diseases</topic><topic>Cytoplasm</topic><topic>Cytoplasm - metabolism</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Enzyme inhibitors</topic><topic>Fluorescence</topic><topic>Glucose</topic><topic>Glucose - metabolism</topic><topic>Glucose transport</topic><topic>Glucose transporter</topic><topic>Glucose Transporter Type 4 - metabolism</topic><topic>Homeostasis</topic><topic>Hygiene</topic><topic>Inhibitors</topic><topic>Insulin</topic><topic>Insulin resistance</topic><topic>Kinases</topic><topic>Laboratories</topic><topic>Life sciences</topic><topic>Liver diseases</topic><topic>MAP kinase</topic><topic>Medicine and Health Sciences</topic><topic>Metabolism</topic><topic>Mice</topic><topic>Nutrition research</topic><topic>Phosphatidylinositol 3-Kinases - 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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>He, Yonghan</au><au>Li, Wen</au><au>Li, Ying</au><au>Zhang, Shuocheng</au><au>Wang, Yanwen</au><au>Sun, Changhao</au><au>Tang, Chih-Hsin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-10-20</date><risdate>2014</risdate><volume>9</volume><issue>10</issue><spage>e110711</spage><epage>e110711</epage><pages>e110711-e110711</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Ursolic acid (UA), a triterpenoid compound, is reported to have a glucose-lowering effect. However, the mechanisms are not fully understood. Adipose tissue is one of peripheral tissues that collectively control the circulating glucose levels.
The objective of the present study was to determine the effect and further the mechanism of action of UA in adipocytes.
The 3T3-L1 preadipocytes were induced to differentiate and treated with different concentrations of UA. NBD-fluorescent glucose was used as the tracer to measure glucose uptake and Western blotting used to determine the expression and activity of proteins involved in glucose transport. It was found that 2.5, 5 and 10 µM of UA promoted glucose uptake in a dose-dependent manner (17%, 29% and 35%, respectively). 10 µM UA-induced glucose uptake with insulin stimulation was completely blocked by the phosphatidylinositol (PI) 3-kinase (PI3K) inhibitor wortmannin (1 µM), but not by SB203580 (10 µM), the inhibitor of mitogen-activated protein kinase (MAPK), or compound C (2.5 µM), the inhibitor of AMP-activated kinase (AMPK) inhibitor. Furthermore, the downstream protein activities of the PI3K pathway, phosphoinositide-dependent kinase (PDK) and phosphoinositide-dependent serine/threoninekinase (AKT) were increased by 10 µM of UA in the presence of insulin. Interestingly, the activity of AS160 and protein kinase C (PKC) and the expression of glucose transporter 4 (GLUT4) were stimulated by 10 µM of UA under either the basal or insulin-stimulated status. Moreover, the translocation of GLUT4 from cytoplasm to cell membrane was increased by UA but decreased when the PI3K inhibitor was applied.
Our results suggest that UA stimulates glucose uptake in 3T3-L1 adipocytes through the PI3K pathway, providing important information regarding the mechanism of action of UA for its anti-diabetic effect.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25329874</pmid><doi>10.1371/journal.pone.0110711</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1614379602 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase 3T3-L1 Cells Acids Adipocytes Adipocytes - cytology Adipocytes - metabolism Adipose tissue AKT protein AMP Animals Anti-Infective Agents - pharmacology Biology and Life Sciences Cell Membrane - metabolism Councils Crop diseases Cytoplasm Cytoplasm - metabolism Diabetes Diabetes mellitus Enzyme inhibitors Fluorescence Glucose Glucose - metabolism Glucose transport Glucose transporter Glucose Transporter Type 4 - metabolism Homeostasis Hygiene Inhibitors Insulin Insulin resistance Kinases Laboratories Life sciences Liver diseases MAP kinase Medicine and Health Sciences Metabolism Mice Nutrition research Phosphatidylinositol 3-Kinases - metabolism Preadipocytes Protein kinase C Protein Kinase Inhibitors - pharmacology Protein Transport - drug effects Proteins Public health Rodents Signal transduction Signal Transduction - drug effects Signaling Tissues Translocation Triterpenes - pharmacology Ursolic Acid Western blotting Wortmannin |
| title | Ursolic acid increases glucose uptake through the PI3K signaling pathway in adipocytes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-09T19%3A26%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ursolic%20acid%20increases%20glucose%20uptake%20through%20the%20PI3K%20signaling%20pathway%20in%20adipocytes&rft.jtitle=PloS%20one&rft.au=He,%20Yonghan&rft.date=2014-10-20&rft.volume=9&rft.issue=10&rft.spage=e110711&rft.epage=e110711&rft.pages=e110711-e110711&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0110711&rft_dat=%3Cgale_plos_%3EA418139311%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1614379602&rft_id=info:pmid/25329874&rft_galeid=A418139311&rft_doaj_id=oai_doaj_org_article_1ab726d7763240c3bca5b2e497200049&rfr_iscdi=true |