Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance
Although activation of the mammalian target of rapamycin complex/p70 S6 kinase (S6K1) pathway by leucine is efficient to stimulate muscle protein synthesis, it can also exert inhibition on the early steps of insulin signaling leading to insulin resistance. We investigated the impact of 5-week leucin...
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| creator | Balage, Michèle Dupont, Joëlle Mothe-Satney, Isabelle Tesseraud, Sophie Mosoni, Laurent Dardevet, Dominique |
| description | Although activation of the mammalian target of rapamycin complex/p70 S6 kinase (S6K1) pathway by leucine is efficient to stimulate muscle protein synthesis, it can also exert inhibition on the early steps of insulin signaling leading to insulin resistance. We investigated the impact of 5-week leucine supplementation on insulin signaling and sensitivity in 4-month old rats fed a 15% protein diet supplemented (LEU) or not (C) with 4.5% leucine. An oral glucose tolerance test was performed in each rat at the end of the supplementation and glucose transport was measured in vitro using isolated epitrochlearis muscles incubated with 2-deoxy-
d-[
3H]-glucose under increasing insulin concentrations. Insulin signaling was assessed on gastrocnemius at the postabsorptive state or 30 and 60 min after gavage with a nutrient bolus. Tyrosine phosphorylation of IRβ, IRS1 and PI3 kinase activity were reduced in LEU group 30 min after feeding (−36%, −36% and −38% respectively,
P |
| doi_str_mv | 10.1016/j.jnutbio.2010.02.001 |
| format | Article |
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d-[
3H]-glucose under increasing insulin concentrations. Insulin signaling was assessed on gastrocnemius at the postabsorptive state or 30 and 60 min after gavage with a nutrient bolus. Tyrosine phosphorylation of IRβ, IRS1 and PI3 kinase activity were reduced in LEU group 30 min after feeding (−36%, −36% and −38% respectively,
P<.05) whereas S6K1, S6rp and 4EBP1 phosphorylations were similar. Overall glucose tolerance was reduced in leucine-supplemented rats and was associated with accumulation of perirenal adipose tissue (+27%,
P<.05). Conversely, in vitro insulin-response of muscle glucose transport tended to be improved in leucine-supplemented rats. In conclusion, dietary leucine supplementation in adult rats induced a delay in the postprandial stimulation in the early steps of muscle insulin signaling without muscle resistance on insulin-induced glucose uptake. However, it resulted in overall glucose intolerance linked to increased local adiposity. Further investigations are necessary to clearly define the beneficial and/or deleterious effects of chronic dietary leucine supplementation in healthy subjects.</description><identifier>ISSN: 0955-2863</identifier><identifier>EISSN: 1873-4847</identifier><identifier>DOI: 10.1016/j.jnutbio.2010.02.001</identifier><identifier>PMID: 20558053</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Adipose Tissue - metabolism ; Animals ; Biological and medical sciences ; Dietary Supplements ; Feeding. Feeding behavior ; Fundamental and applied biological sciences. Psychology ; Glucose - metabolism ; Glucose Intolerance - chemically induced ; Glucose Intolerance - metabolism ; Glucose tolerance ; Glucose Tolerance Test ; Insulin ; Insulin - blood ; Insulin - metabolism ; Insulin Receptor Substrate Proteins - metabolism ; Insulin Resistance ; Leucine ; Leucine - pharmacology ; Life Sciences ; Linear Models ; Male ; Muscle, Skeletal - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Phosphorylation ; Rat ; Rats ; Rats, Wistar ; Receptor, Insulin - metabolism ; Ribosomal Protein S6 Kinases, 70-kDa - metabolism ; Signal Transduction ; Signaling ; Sirolimus - pharmacology ; TOR Serine-Threonine Kinases - metabolism ; Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><ispartof>The Journal of nutritional biochemistry, 2011-03, Vol.22 (3), p.219-226</ispartof><rights>2011 Elsevier Inc.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c452t-30acbdef97d7c24c8bf37d16f10549ea6fb049b47c19a96502a80f67f06c41c53</citedby><orcidid>0000-0003-0305-1885 ; 0000-0002-8046-7705 ; 0000-0002-5409-6760 ; 0000-0001-7320-9970</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0955286310000495$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23953386$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20558053$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01129576$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Balage, Michèle</creatorcontrib><creatorcontrib>Dupont, Joëlle</creatorcontrib><creatorcontrib>Mothe-Satney, Isabelle</creatorcontrib><creatorcontrib>Tesseraud, Sophie</creatorcontrib><creatorcontrib>Mosoni, Laurent</creatorcontrib><creatorcontrib>Dardevet, Dominique</creatorcontrib><title>Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance</title><title>The Journal of nutritional biochemistry</title><addtitle>J Nutr Biochem</addtitle><description>Although activation of the mammalian target of rapamycin complex/p70 S6 kinase (S6K1) pathway by leucine is efficient to stimulate muscle protein synthesis, it can also exert inhibition on the early steps of insulin signaling leading to insulin resistance. We investigated the impact of 5-week leucine supplementation on insulin signaling and sensitivity in 4-month old rats fed a 15% protein diet supplemented (LEU) or not (C) with 4.5% leucine. An oral glucose tolerance test was performed in each rat at the end of the supplementation and glucose transport was measured in vitro using isolated epitrochlearis muscles incubated with 2-deoxy-
d-[
3H]-glucose under increasing insulin concentrations. Insulin signaling was assessed on gastrocnemius at the postabsorptive state or 30 and 60 min after gavage with a nutrient bolus. Tyrosine phosphorylation of IRβ, IRS1 and PI3 kinase activity were reduced in LEU group 30 min after feeding (−36%, −36% and −38% respectively,
P<.05) whereas S6K1, S6rp and 4EBP1 phosphorylations were similar. Overall glucose tolerance was reduced in leucine-supplemented rats and was associated with accumulation of perirenal adipose tissue (+27%,
P<.05). Conversely, in vitro insulin-response of muscle glucose transport tended to be improved in leucine-supplemented rats. In conclusion, dietary leucine supplementation in adult rats induced a delay in the postprandial stimulation in the early steps of muscle insulin signaling without muscle resistance on insulin-induced glucose uptake. However, it resulted in overall glucose intolerance linked to increased local adiposity. Further investigations are necessary to clearly define the beneficial and/or deleterious effects of chronic dietary leucine supplementation in healthy subjects.</description><subject>Adipose Tissue - metabolism</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Dietary Supplements</subject><subject>Feeding. Feeding behavior</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Glucose - metabolism</subject><subject>Glucose Intolerance - chemically induced</subject><subject>Glucose Intolerance - metabolism</subject><subject>Glucose tolerance</subject><subject>Glucose Tolerance Test</subject><subject>Insulin</subject><subject>Insulin - blood</subject><subject>Insulin - metabolism</subject><subject>Insulin Receptor Substrate Proteins - metabolism</subject><subject>Insulin Resistance</subject><subject>Leucine</subject><subject>Leucine - pharmacology</subject><subject>Life Sciences</subject><subject>Linear Models</subject><subject>Male</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Phosphorylation</subject><subject>Rat</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Receptor, Insulin - metabolism</subject><subject>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Sirolimus - pharmacology</subject><subject>TOR Serine-Threonine Kinases - metabolism</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><issn>0955-2863</issn><issn>1873-4847</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc-O0zAQhy0EYkvhEQBfEOLQ7tix8-eEVitgKyqBgD1bE8dpXTlxNna62hfguXGVshy5eKSfv_FY8xHymsGaAcsvD-tDP8Xa-jWHlAFfA7AnZMHKIluJUhRPyQIqKVe8zLML8iKEAwBwIfPn5IKDlCXIbEF-b82kbW9omIbBmc70EaP1PbU9HTGGVJtJm4YibYzDh1PeTUE7Qzc_Lr9vsq802F2PzvY7OmDc3ycGQ_DaYkxt9zbuqT-aEZ2jthvQjinduUn7YGj0Lt302rwkz1p0wbw61yW5_fzp1_XNavvty-b6arvSQvK4ygB13Zi2KppCc6HLus2KhuUtAykqg3lbg6hqUWhWYZVL4FhCmxct5FowLbMl-TC_u0enhtF2OD4oj1bdXG3VKQPGeCWL_MgS-35mh9HfTSZE1dmgjXPYGz8FVcqM80xAkUg5k3r0IYymfXyagTrZUgd1tqVOthRwlWylvjfnCVPdmeax66-eBLw7Axg0uva0Kxv-cVmVoOR3Sd7OXIte4W5MzO3PNCkDVok8HYn4OBMmbfdozaiCtiZtvklCdFSNt__57B9IksAK</recordid><startdate>20110301</startdate><enddate>20110301</enddate><creator>Balage, Michèle</creator><creator>Dupont, Joëlle</creator><creator>Mothe-Satney, Isabelle</creator><creator>Tesseraud, Sophie</creator><creator>Mosoni, Laurent</creator><creator>Dardevet, Dominique</creator><general>Elsevier Inc</general><general>New York, NY: Elsevier Science</general><general>Elsevier</general><scope>FBQ</scope><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>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0003-0305-1885</orcidid><orcidid>https://orcid.org/0000-0002-8046-7705</orcidid><orcidid>https://orcid.org/0000-0002-5409-6760</orcidid><orcidid>https://orcid.org/0000-0001-7320-9970</orcidid></search><sort><creationdate>20110301</creationdate><title>Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance</title><author>Balage, Michèle ; Dupont, Joëlle ; Mothe-Satney, Isabelle ; Tesseraud, Sophie ; Mosoni, Laurent ; Dardevet, Dominique</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-30acbdef97d7c24c8bf37d16f10549ea6fb049b47c19a96502a80f67f06c41c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adipose Tissue - metabolism</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Dietary Supplements</topic><topic>Feeding. Feeding behavior</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Glucose - metabolism</topic><topic>Glucose Intolerance - chemically induced</topic><topic>Glucose Intolerance - metabolism</topic><topic>Glucose tolerance</topic><topic>Glucose Tolerance Test</topic><topic>Insulin</topic><topic>Insulin - blood</topic><topic>Insulin - metabolism</topic><topic>Insulin Receptor Substrate Proteins - metabolism</topic><topic>Insulin Resistance</topic><topic>Leucine</topic><topic>Leucine - pharmacology</topic><topic>Life Sciences</topic><topic>Linear Models</topic><topic>Male</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Phosphorylation</topic><topic>Rat</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Receptor, Insulin - metabolism</topic><topic>Ribosomal Protein S6 Kinases, 70-kDa - metabolism</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Sirolimus - pharmacology</topic><topic>TOR Serine-Threonine Kinases - metabolism</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Balage, Michèle</creatorcontrib><creatorcontrib>Dupont, Joëlle</creatorcontrib><creatorcontrib>Mothe-Satney, Isabelle</creatorcontrib><creatorcontrib>Tesseraud, Sophie</creatorcontrib><creatorcontrib>Mosoni, Laurent</creatorcontrib><creatorcontrib>Dardevet, Dominique</creatorcontrib><collection>AGRIS</collection><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>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>The Journal of nutritional biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Balage, Michèle</au><au>Dupont, Joëlle</au><au>Mothe-Satney, Isabelle</au><au>Tesseraud, Sophie</au><au>Mosoni, Laurent</au><au>Dardevet, Dominique</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance</atitle><jtitle>The Journal of nutritional biochemistry</jtitle><addtitle>J Nutr Biochem</addtitle><date>2011-03-01</date><risdate>2011</risdate><volume>22</volume><issue>3</issue><spage>219</spage><epage>226</epage><pages>219-226</pages><issn>0955-2863</issn><eissn>1873-4847</eissn><abstract>Although activation of the mammalian target of rapamycin complex/p70 S6 kinase (S6K1) pathway by leucine is efficient to stimulate muscle protein synthesis, it can also exert inhibition on the early steps of insulin signaling leading to insulin resistance. We investigated the impact of 5-week leucine supplementation on insulin signaling and sensitivity in 4-month old rats fed a 15% protein diet supplemented (LEU) or not (C) with 4.5% leucine. An oral glucose tolerance test was performed in each rat at the end of the supplementation and glucose transport was measured in vitro using isolated epitrochlearis muscles incubated with 2-deoxy-
d-[
3H]-glucose under increasing insulin concentrations. Insulin signaling was assessed on gastrocnemius at the postabsorptive state or 30 and 60 min after gavage with a nutrient bolus. Tyrosine phosphorylation of IRβ, IRS1 and PI3 kinase activity were reduced in LEU group 30 min after feeding (−36%, −36% and −38% respectively,
P<.05) whereas S6K1, S6rp and 4EBP1 phosphorylations were similar. Overall glucose tolerance was reduced in leucine-supplemented rats and was associated with accumulation of perirenal adipose tissue (+27%,
P<.05). Conversely, in vitro insulin-response of muscle glucose transport tended to be improved in leucine-supplemented rats. In conclusion, dietary leucine supplementation in adult rats induced a delay in the postprandial stimulation in the early steps of muscle insulin signaling without muscle resistance on insulin-induced glucose uptake. However, it resulted in overall glucose intolerance linked to increased local adiposity. Further investigations are necessary to clearly define the beneficial and/or deleterious effects of chronic dietary leucine supplementation in healthy subjects.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>20558053</pmid><doi>10.1016/j.jnutbio.2010.02.001</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-0305-1885</orcidid><orcidid>https://orcid.org/0000-0002-8046-7705</orcidid><orcidid>https://orcid.org/0000-0002-5409-6760</orcidid><orcidid>https://orcid.org/0000-0001-7320-9970</orcidid></addata></record> |
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| subjects | Adipose Tissue - metabolism Animals Biological and medical sciences Dietary Supplements Feeding. Feeding behavior Fundamental and applied biological sciences. Psychology Glucose - metabolism Glucose Intolerance - chemically induced Glucose Intolerance - metabolism Glucose tolerance Glucose Tolerance Test Insulin Insulin - blood Insulin - metabolism Insulin Receptor Substrate Proteins - metabolism Insulin Resistance Leucine Leucine - pharmacology Life Sciences Linear Models Male Muscle, Skeletal - metabolism Phosphatidylinositol 3-Kinases - metabolism Phosphorylation Rat Rats Rats, Wistar Receptor, Insulin - metabolism Ribosomal Protein S6 Kinases, 70-kDa - metabolism Signal Transduction Signaling Sirolimus - pharmacology TOR Serine-Threonine Kinases - metabolism Vertebrates: anatomy and physiology, studies on body, several organs or systems |
| title | Leucine supplementation in rats induced a delay in muscle IR/PI3K signaling pathway associated with overall impaired glucose tolerance |
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