Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice
Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effe...
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| Veröffentlicht in: | PloS one 2013-12, Vol.8 (12), p.e83264-e83264 |
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| creator | Wang, Ting Kusudo, Tatsuya Takeuchi, Tamaki Yamashita, Yukari Kontani, Yasuhide Okamatsu, Yuko Saito, Masayuki Mori, Nozomu Yamashita, Hitoshi |
| description | Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes. |
| doi_str_mv | 10.1371/journal.pone.0083264 |
| format | Article |
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This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0083264</identifier><identifier>PMID: 24391749</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>3T3-L1 Cells ; Adipocytes ; Adipocytes - drug effects ; Adipocytes - metabolism ; Adipose tissue ; Adipose Tissue, White - drug effects ; Adipose Tissue, White - metabolism ; AKT protein ; AMP ; AMP-activated protein kinase ; AMP-Activated Protein Kinases - metabolism ; Animals ; Biology ; Cellular signal transduction ; Diabetes mellitus ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - metabolism ; Down-regulation ; Energy metabolism ; Evodia - chemistry ; Feedback loops ; Female ; Glucose ; Glucose - metabolism ; Glucose tolerance ; Glucose Tolerance Test ; Hypoglycemic Agents - pharmacology ; Insulin ; Insulin receptor substrate 1 ; Insulin Receptor Substrate Proteins - antagonists & inhibitors ; Insulin Receptor Substrate Proteins - chemistry ; Insulin Receptor Substrate Proteins - metabolism ; Insulin Resistance ; Kinases ; Materials Science ; Medicine ; Metabolism ; Mice ; Mice, Obese ; Negative feedback ; Obesity ; Phosphorylation ; Phosphorylation - drug effects ; Physiological aspects ; Protein kinases ; Quinazolines - pharmacology ; Rapamycin ; Ribosomal protein S6 ; Ribosomal Protein S6 Kinases - antagonists & inhibitors ; Rodents ; Rosiglitazone ; Serine ; Serine - chemistry ; Signal transduction ; Signal Transduction - drug effects ; Signaling ; Substrates ; TOR protein ; TOR Serine-Threonine Kinases - antagonists & inhibitors ; Transduction ; Type 2 diabetes</subject><ispartof>PloS one, 2013-12, Vol.8 (12), p.e83264-e83264</ispartof><rights>COPYRIGHT 2013 Public Library of Science</rights><rights>2013 Wang 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>2013 Wang et al 2013 Wang et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c802t-ec48b3c746a412b2c04f54c9be957bc4de7e95f71ac9c6362486aafd356d28a43</citedby><cites>FETCH-LOGICAL-c802t-ec48b3c746a412b2c04f54c9be957bc4de7e95f71ac9c6362486aafd356d28a43</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/PMC3877036/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3877036/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23868,27926,27927,53793,53795</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24391749$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stadler, Krisztian</contributor><creatorcontrib>Wang, Ting</creatorcontrib><creatorcontrib>Kusudo, Tatsuya</creatorcontrib><creatorcontrib>Takeuchi, Tamaki</creatorcontrib><creatorcontrib>Yamashita, Yukari</creatorcontrib><creatorcontrib>Kontani, Yasuhide</creatorcontrib><creatorcontrib>Okamatsu, Yuko</creatorcontrib><creatorcontrib>Saito, Masayuki</creatorcontrib><creatorcontrib>Mori, Nozomu</creatorcontrib><creatorcontrib>Yamashita, Hitoshi</creatorcontrib><title>Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes.</description><subject>3T3-L1 Cells</subject><subject>Adipocytes</subject><subject>Adipocytes - drug effects</subject><subject>Adipocytes - metabolism</subject><subject>Adipose tissue</subject><subject>Adipose Tissue, White - drug effects</subject><subject>Adipose Tissue, White - metabolism</subject><subject>AKT protein</subject><subject>AMP</subject><subject>AMP-activated protein kinase</subject><subject>AMP-Activated Protein Kinases - metabolism</subject><subject>Animals</subject><subject>Biology</subject><subject>Cellular signal transduction</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Down-regulation</subject><subject>Energy metabolism</subject><subject>Evodia - chemistry</subject><subject>Feedback loops</subject><subject>Female</subject><subject>Glucose</subject><subject>Glucose - metabolism</subject><subject>Glucose tolerance</subject><subject>Glucose Tolerance Test</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Insulin</subject><subject>Insulin receptor substrate 1</subject><subject>Insulin Receptor Substrate Proteins - antagonists & inhibitors</subject><subject>Insulin Receptor Substrate Proteins - chemistry</subject><subject>Insulin Receptor Substrate Proteins - metabolism</subject><subject>Insulin Resistance</subject><subject>Kinases</subject><subject>Materials Science</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Mice</subject><subject>Mice, Obese</subject><subject>Negative feedback</subject><subject>Obesity</subject><subject>Phosphorylation</subject><subject>Phosphorylation - drug effects</subject><subject>Physiological aspects</subject><subject>Protein kinases</subject><subject>Quinazolines - pharmacology</subject><subject>Rapamycin</subject><subject>Ribosomal protein S6</subject><subject>Ribosomal Protein S6 Kinases - antagonists & inhibitors</subject><subject>Rodents</subject><subject>Rosiglitazone</subject><subject>Serine</subject><subject>Serine - chemistry</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Signaling</subject><subject>Substrates</subject><subject>TOR protein</subject><subject>TOR Serine-Threonine Kinases - antagonists & inhibitors</subject><subject>Transduction</subject><subject>Type 2 diabetes</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</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>eNqNk11rFDEUhgdRrFb_geiAIHqx23xNMnMjlFJ1sVBoq7chk5zZTclM1iSz2D_jbzXT3Zau9EKGYc4kz_uek49TFG8wmmMq8NG1H8Og3HztB5gjVFPC2ZPiBW4omXGC6NMH8UHxMsZrhCpac_68OCCMNliw5kXx53TjjVW9HaC0w8q2NsUcxNHZYRaT7UenEpiyvzq_mF3y76XSyW5Usn4o1WDKxcUlLiOESb9e-ZjfcOO28zYjxq69vkkQb2nbr4Pf5J-lG7WPUCbvIKhBT8lL30KEo1xNC8nqsrcaXhXPOuUivN59D4sfX06vTr7Nzs6_Lk6Oz2a6RiTNQLO6pVowrhgmLdGIdRXTTQtNJVrNDIgcdQIr3WhOOWE1V6oztOKG1IrRw-Ld1nftfJS7rY0SM0Epw4jTTCy2hPHqWq6D7VW4kV5ZeTvgw1KqkMt2IFtBSdWZpuINZYaAEhVQJOquM7zFAmWvz7tsY9uD0TCkoNye6f7MYFdy6TeS1iLLeTb4uDMI_tcIMcneRg3OqQH8ONXdIN4IWomMvv8HfXx1O2qp8gLs0PmcV0-m8pgJ0RBBcJWp-SNUfgzkw8r3sLN5fE_waU-QmQS_01KNMcrF5cX_s-c_99kPD9gVKJdW0btxunZxH2RbUAcfY4DufpMxklMb3e2GnNpI7tooy94-PKB70V3f0L8s7Bq4</recordid><startdate>20131231</startdate><enddate>20131231</enddate><creator>Wang, Ting</creator><creator>Kusudo, Tatsuya</creator><creator>Takeuchi, Tamaki</creator><creator>Yamashita, Yukari</creator><creator>Kontani, Yasuhide</creator><creator>Okamatsu, Yuko</creator><creator>Saito, Masayuki</creator><creator>Mori, Nozomu</creator><creator>Yamashita, Hitoshi</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>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>20131231</creationdate><title>Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice</title><author>Wang, Ting ; Kusudo, Tatsuya ; Takeuchi, Tamaki ; Yamashita, Yukari ; Kontani, Yasuhide ; Okamatsu, Yuko ; Saito, Masayuki ; Mori, Nozomu ; Yamashita, Hitoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c802t-ec48b3c746a412b2c04f54c9be957bc4de7e95f71ac9c6362486aafd356d28a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>3T3-L1 Cells</topic><topic>Adipocytes</topic><topic>Adipocytes - 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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - 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>Wang, Ting</au><au>Kusudo, Tatsuya</au><au>Takeuchi, Tamaki</au><au>Yamashita, Yukari</au><au>Kontani, Yasuhide</au><au>Okamatsu, Yuko</au><au>Saito, Masayuki</au><au>Mori, Nozomu</au><au>Yamashita, Hitoshi</au><au>Stadler, Krisztian</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2013-12-31</date><risdate>2013</risdate><volume>8</volume><issue>12</issue><spage>e83264</spage><epage>e83264</epage><pages>e83264-e83264</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24391749</pmid><doi>10.1371/journal.pone.0083264</doi><tpages>e83264</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2013-12, Vol.8 (12), p.e83264-e83264 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1473341063 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science website; PubMed Central; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | 3T3-L1 Cells Adipocytes Adipocytes - drug effects Adipocytes - metabolism Adipose tissue Adipose Tissue, White - drug effects Adipose Tissue, White - metabolism AKT protein AMP AMP-activated protein kinase AMP-Activated Protein Kinases - metabolism Animals Biology Cellular signal transduction Diabetes mellitus Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Down-regulation Energy metabolism Evodia - chemistry Feedback loops Female Glucose Glucose - metabolism Glucose tolerance Glucose Tolerance Test Hypoglycemic Agents - pharmacology Insulin Insulin receptor substrate 1 Insulin Receptor Substrate Proteins - antagonists & inhibitors Insulin Receptor Substrate Proteins - chemistry Insulin Receptor Substrate Proteins - metabolism Insulin Resistance Kinases Materials Science Medicine Metabolism Mice Mice, Obese Negative feedback Obesity Phosphorylation Phosphorylation - drug effects Physiological aspects Protein kinases Quinazolines - pharmacology Rapamycin Ribosomal protein S6 Ribosomal Protein S6 Kinases - antagonists & inhibitors Rodents Rosiglitazone Serine Serine - chemistry Signal transduction Signal Transduction - drug effects Signaling Substrates TOR protein TOR Serine-Threonine Kinases - antagonists & inhibitors Transduction Type 2 diabetes |
| title | Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice |
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