Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity
We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted afte...
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| Veröffentlicht in: | Journal of endocrinology 2013-04, Vol.217 (1), p.31-43 |
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| creator | Pereira, Sandra Yu, Wen Qin Frigolet, María E Beaudry, Jacqueline L Shpilberg, Yaniv Park, Edward Dirlea, Cristina Nyomba, B L Grégoire Riddell, Michael C Fantus, I George Giacca, Adria |
| description | We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P |
| doi_str_mv | 10.1530/JOE-12-0214 |
| format | Article |
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We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase.</description><identifier>ISSN: 0022-0795</identifier><identifier>EISSN: 1479-6805</identifier><identifier>DOI: 10.1530/JOE-12-0214</identifier><identifier>PMID: 23328071</identifier><language>eng</language><publisher>England: BioScientifica</publisher><subject>Animals ; Anti-Inflammatory Agents, Non-Steroidal - administration & dosage ; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use ; Disease Models, Animal ; Emulsions ; Fatty Acids, Nonesterified - blood ; Female ; Heparin ; I-kappa B Proteins - antagonists & inhibitors ; I-kappa B Proteins - metabolism ; Infusions, Intravenous ; Insulin Resistance ; Kinetics ; Liver - drug effects ; Liver - metabolism ; Muscle, Skeletal - drug effects ; Muscle, Skeletal - immunology ; Muscle, Skeletal - metabolism ; NF-KappaB Inhibitor alpha ; Obesity - blood ; Obesity - drug therapy ; Obesity - immunology ; Obesity - metabolism ; Phospholipids ; Phosphorylation - drug effects ; Protein Processing, Post-Translational - drug effects ; Random Allocation ; Rats ; Rats, Wistar ; Sodium Salicylate - administration & dosage ; Sodium Salicylate - therapeutic use ; Soybean Oil</subject><ispartof>Journal of endocrinology, 2013-04, Vol.217 (1), p.31-43</ispartof><rights>2013 Society for Endocrinology</rights><rights>2013 Society for Endocrinology 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b423t-9e9ce56fd277a1d3afca14dc1df8ba0ab3afe73d2c6c923af2b6e49b776601753</citedby><cites>FETCH-LOGICAL-b423t-9e9ce56fd277a1d3afca14dc1df8ba0ab3afe73d2c6c923af2b6e49b776601753</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23328071$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pereira, Sandra</creatorcontrib><creatorcontrib>Yu, Wen Qin</creatorcontrib><creatorcontrib>Frigolet, María E</creatorcontrib><creatorcontrib>Beaudry, Jacqueline L</creatorcontrib><creatorcontrib>Shpilberg, Yaniv</creatorcontrib><creatorcontrib>Park, Edward</creatorcontrib><creatorcontrib>Dirlea, Cristina</creatorcontrib><creatorcontrib>Nyomba, B L Grégoire</creatorcontrib><creatorcontrib>Riddell, Michael C</creatorcontrib><creatorcontrib>Fantus, I George</creatorcontrib><creatorcontrib>Giacca, Adria</creatorcontrib><title>Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity</title><title>Journal of endocrinology</title><addtitle>J Endocrinol</addtitle><description>We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase.</description><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</subject><subject>Disease Models, Animal</subject><subject>Emulsions</subject><subject>Fatty Acids, Nonesterified - blood</subject><subject>Female</subject><subject>Heparin</subject><subject>I-kappa B Proteins - antagonists & inhibitors</subject><subject>I-kappa B Proteins - metabolism</subject><subject>Infusions, Intravenous</subject><subject>Insulin Resistance</subject><subject>Kinetics</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Muscle, Skeletal - immunology</subject><subject>Muscle, Skeletal - metabolism</subject><subject>NF-KappaB Inhibitor alpha</subject><subject>Obesity - blood</subject><subject>Obesity - drug therapy</subject><subject>Obesity - immunology</subject><subject>Obesity - metabolism</subject><subject>Phospholipids</subject><subject>Phosphorylation - drug effects</subject><subject>Protein Processing, Post-Translational - drug effects</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Sodium Salicylate - administration & dosage</subject><subject>Sodium Salicylate - therapeutic use</subject><subject>Soybean Oil</subject><issn>0022-0795</issn><issn>1479-6805</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1LAzEQxYMoWqsn75KbB1nNx-5m9yJIrV8UetFzSLITG9nuliQt7H9vSrXoxdMwM-_9HjyELii5oQUnt6_zaUZZRhjND9CI5qLOyooUh2hECEt3URcn6DSET0JoQQU_RieMc1YRQUdIP6y9iq7vcG-xdwGw67D1ANiqGAesjGsCbiCCX7oOAg6qdWZoVYSrgMFaMBEn9wJWCWOSO6zbhAjQBRfdxsXhDB1Z1QY4_55j9P44fZs8Z7P508vkfpbpnPGY1VAbKErbMCEUbbiyRtG8MbSxlVZE6XQBwRtmSlOztDBdQl5rIcqSUFHwMbrbcVdrvYTGQBe9auXKu6Xyg-yVk38_nVvIj34jefJXpE6A6x3A-D4ED3bvpURuq5apakmZ3Fad1Je_4_ban26TgO4E2vXBuBTqrDPqX-gXqmmNbg</recordid><startdate>201304</startdate><enddate>201304</enddate><creator>Pereira, Sandra</creator><creator>Yu, Wen Qin</creator><creator>Frigolet, María E</creator><creator>Beaudry, Jacqueline L</creator><creator>Shpilberg, Yaniv</creator><creator>Park, Edward</creator><creator>Dirlea, Cristina</creator><creator>Nyomba, B L Grégoire</creator><creator>Riddell, Michael C</creator><creator>Fantus, I George</creator><creator>Giacca, Adria</creator><general>BioScientifica</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>5PM</scope></search><sort><creationdate>201304</creationdate><title>Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity</title><author>Pereira, Sandra ; Yu, Wen Qin ; Frigolet, María E ; Beaudry, Jacqueline L ; Shpilberg, Yaniv ; Park, Edward ; Dirlea, Cristina ; Nyomba, B L Grégoire ; Riddell, Michael C ; Fantus, I George ; Giacca, Adria</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b423t-9e9ce56fd277a1d3afca14dc1df8ba0ab3afe73d2c6c923af2b6e49b776601753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - administration & dosage</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - therapeutic use</topic><topic>Disease Models, Animal</topic><topic>Emulsions</topic><topic>Fatty Acids, Nonesterified - blood</topic><topic>Female</topic><topic>Heparin</topic><topic>I-kappa B Proteins - antagonists & inhibitors</topic><topic>I-kappa B Proteins - metabolism</topic><topic>Infusions, Intravenous</topic><topic>Insulin Resistance</topic><topic>Kinetics</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Muscle, Skeletal - immunology</topic><topic>Muscle, Skeletal - metabolism</topic><topic>NF-KappaB Inhibitor alpha</topic><topic>Obesity - blood</topic><topic>Obesity - drug therapy</topic><topic>Obesity - immunology</topic><topic>Obesity - metabolism</topic><topic>Phospholipids</topic><topic>Phosphorylation - drug effects</topic><topic>Protein Processing, Post-Translational - drug effects</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Sodium Salicylate - administration & dosage</topic><topic>Sodium Salicylate - therapeutic use</topic><topic>Soybean Oil</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pereira, Sandra</creatorcontrib><creatorcontrib>Yu, Wen Qin</creatorcontrib><creatorcontrib>Frigolet, María E</creatorcontrib><creatorcontrib>Beaudry, Jacqueline L</creatorcontrib><creatorcontrib>Shpilberg, Yaniv</creatorcontrib><creatorcontrib>Park, Edward</creatorcontrib><creatorcontrib>Dirlea, Cristina</creatorcontrib><creatorcontrib>Nyomba, B L Grégoire</creatorcontrib><creatorcontrib>Riddell, Michael C</creatorcontrib><creatorcontrib>Fantus, I George</creatorcontrib><creatorcontrib>Giacca, Adria</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of endocrinology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pereira, Sandra</au><au>Yu, Wen Qin</au><au>Frigolet, María E</au><au>Beaudry, Jacqueline L</au><au>Shpilberg, Yaniv</au><au>Park, Edward</au><au>Dirlea, Cristina</au><au>Nyomba, B L Grégoire</au><au>Riddell, Michael C</au><au>Fantus, I George</au><au>Giacca, Adria</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity</atitle><jtitle>Journal of endocrinology</jtitle><addtitle>J Endocrinol</addtitle><date>2013-04</date><risdate>2013</risdate><volume>217</volume><issue>1</issue><spage>31</spage><epage>43</epage><pages>31-43</pages><issn>0022-0795</issn><eissn>1479-6805</eissn><abstract>We have shown in rats that sodium salicylate (SS), which inhibits IkBa kinase B (IKKB), prevents hepatic and peripheral insulin resistance caused by short-term (7 h) i.v. administration of Intralipid and heparin (IH). We wished to further determine whether this beneficial effect of SS persisted after prolonged (48 h) IH infusion, which better mimics the chronic free fatty acid (FFA) elevation of obesity. Hence, we performed hyperinsulinemic euglycemic clamps with tritiated glucose methodology to determine hepatic and peripheral insulin sensitivity in rats infused with saline, IH, IH and SS, or SS alone. SS prevented peripheral insulin resistance (P<0.05) caused by prolonged plasma FFA elevation; however, it did not prevent hepatic insulin resistance. In skeletal muscle, protein levels of phospho-IkBa were augmented by prolonged IH administration and this was prevented by SS, suggesting that IH activates while SS prevents the activation of IKKB. Markers of IKKB activation, namely protein levels of phospho-IkBa and IkBa, indicated that IKKB is not activated in the liver after prolonged FFA elevation. Phosphorylation of serine 307 at insulin receptor substrate (IRS)-1, which is a marker of proximal insulin resistance, was not altered by IH administration in the liver, suggesting that this is not a site of hepatic insulin resistance in the prolonged lipid infusion model. Our results suggest that the role of IKKB in fat-induced insulin resistance is time and tissue dependent and that hepatic insulin resistance induced by prolonged lipid elevation is not due to an IRS-1 serine 307 kinase.</abstract><cop>England</cop><pub>BioScientifica</pub><pmid>23328071</pmid><doi>10.1530/JOE-12-0214</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Anti-Inflammatory Agents, Non-Steroidal - administration & dosage Anti-Inflammatory Agents, Non-Steroidal - therapeutic use Disease Models, Animal Emulsions Fatty Acids, Nonesterified - blood Female Heparin I-kappa B Proteins - antagonists & inhibitors I-kappa B Proteins - metabolism Infusions, Intravenous Insulin Resistance Kinetics Liver - drug effects Liver - metabolism Muscle, Skeletal - drug effects Muscle, Skeletal - immunology Muscle, Skeletal - metabolism NF-KappaB Inhibitor alpha Obesity - blood Obesity - drug therapy Obesity - immunology Obesity - metabolism Phospholipids Phosphorylation - drug effects Protein Processing, Post-Translational - drug effects Random Allocation Rats Rats, Wistar Sodium Salicylate - administration & dosage Sodium Salicylate - therapeutic use Soybean Oil |
| title | Duration of rise in free fatty acids determines salicylate's effect on hepatic insulin sensitivity |
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