Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans
Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans Oliver P. Bachmann 1 , Dominik B. Dahl 1 , Klaus Brechtel 2 , Jürgen Machann 2 , Michael Haap 1 , Thomas Maier 1 , Mattias Loviscach 1 , Michael Stumvoll 1 , Claus...
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Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2001-11, Vol.50 (11), p.2579-2584 |
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creator | Bachmann, O P Dahl, D B Brechtel, K Machann, J Haap, M Maier, T Loviscach, M Stumvoll, M Claussen, C D Schick, F Häring, H U Jacob, S |
description | Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity
in Humans
Oliver P. Bachmann 1 ,
Dominik B. Dahl 1 ,
Klaus Brechtel 2 ,
Jürgen Machann 2 ,
Michael Haap 1 ,
Thomas Maier 1 ,
Mattias Loviscach 1 ,
Michael Stumvoll 1 ,
Claus D. Claussen 2 ,
Fritz Schick 2 ,
Hans U. Häring 1 and
Stephan Jacob 1
1 Department of Endocrinology and Metabolism, Eberhard-Karls University, Tübingen, Germany, and
2 Department of Radiology, Eberhard-Karls University, Tübingen, Germany
Abstract
An increased intramyocellular lipid (IMCL) content, as quantified by 1 H-magnetic resonance spectroscopy ( 1 H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and
how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating
nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a
high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic
glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by 1 H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly
after 2 h, reaching a maximum of 120.8 ± 3.4% (SOL) and 164.2 ± 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 ± 5.4% of baseline
after 6 h. Over time, the GIR was strongly correlated with IMCL in TA ( r = −0.98, P ≤ 0.003) and SOL muscle ( r = −0.97, P ≤ 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after
completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased
significantly in TA muscle (to 148.0 ± 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 ± 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 ± 5.6% of baseline
( P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of
the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion
protocol suggest a functional relationship between IMCL levels and insulin sens |
doi_str_mv | 10.2337/diabetes.50.11.2579 |
format | Article |
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in Humans
Oliver P. Bachmann 1 ,
Dominik B. Dahl 1 ,
Klaus Brechtel 2 ,
Jürgen Machann 2 ,
Michael Haap 1 ,
Thomas Maier 1 ,
Mattias Loviscach 1 ,
Michael Stumvoll 1 ,
Claus D. Claussen 2 ,
Fritz Schick 2 ,
Hans U. Häring 1 and
Stephan Jacob 1
1 Department of Endocrinology and Metabolism, Eberhard-Karls University, Tübingen, Germany, and
2 Department of Radiology, Eberhard-Karls University, Tübingen, Germany
Abstract
An increased intramyocellular lipid (IMCL) content, as quantified by 1 H-magnetic resonance spectroscopy ( 1 H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and
how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating
nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a
high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic
glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by 1 H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly
after 2 h, reaching a maximum of 120.8 ± 3.4% (SOL) and 164.2 ± 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 ± 5.4% of baseline
after 6 h. Over time, the GIR was strongly correlated with IMCL in TA ( r = −0.98, P ≤ 0.003) and SOL muscle ( r = −0.97, P ≤ 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after
completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased
significantly in TA muscle (to 148.0 ± 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 ± 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 ± 5.6% of baseline
( P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of
the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion
protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by
a high-fat diet, thereby underlining the physiological relevance of these observations.
Footnotes
Address correspondence and reprint requests to Dr. Hans U. Häring, Medical Clinic, Department of Endocrinology and Metabolism,
Otfried-Müller Str. 10, D-72076, Tübingen, Germany. E-mail: hans-ulrich.haering{at}med.uni-tuebingen.de
O.P.B. and D.B.D. contributed equally to the article.
Received for publication 5 March 2001 and accepted in revised form 7 August 2001.
CT, computed tomography; GIR, glucose infusion rate; IMCL, intramyocellular lipid; 1 H-MRS, 1 H-magnetic resonance spectroscopy; NEFA, nonesterified fatty acid; SOL, soleus; TA, tibialis anterior.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/diabetes.50.11.2579</identifier><identifier>PMID: 11679437</identifier><identifier>CODEN: DIAEAZ</identifier><language>eng</language><publisher>Alexandria, VA: American Diabetes Association</publisher><subject>Adult ; Biological and medical sciences ; Blood Glucose - analysis ; Diabetes ; Diabetes research ; Diabetes. Impaired glucose tolerance ; Diet ; Dietary Fats - pharmacology ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Fatty acids ; Fatty Acids, Nonesterified - blood ; Glucose ; Health aspects ; Humans ; Injections, Intravenous ; Insulin - blood ; Insulin - physiology ; Insulin resistance ; Lipid Metabolism ; Lipids ; Lipids - pharmacology ; Male ; Medical sciences ; Metabolism ; Muscle, Skeletal - cytology ; Muscle, Skeletal - metabolism ; Musculoskeletal system ; NMR ; Nuclear magnetic resonance ; Pathogenesis ; Spectrum analysis ; Type 2 diabetes</subject><ispartof>Diabetes (New York, N.Y.), 2001-11, Vol.50 (11), p.2579-2584</ispartof><rights>2002 INIST-CNRS</rights><rights>COPYRIGHT 2001 American Diabetes Association</rights><rights>Copyright American Diabetes Association Nov 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c589t-a177b518333ede198f7c234aa6f45c82e8b71b45a8658424bd0f35454b1aa74b3</citedby><cites>FETCH-LOGICAL-c589t-a177b518333ede198f7c234aa6f45c82e8b71b45a8658424bd0f35454b1aa74b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14149961$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11679437$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bachmann, O P</creatorcontrib><creatorcontrib>Dahl, D B</creatorcontrib><creatorcontrib>Brechtel, K</creatorcontrib><creatorcontrib>Machann, J</creatorcontrib><creatorcontrib>Haap, M</creatorcontrib><creatorcontrib>Maier, T</creatorcontrib><creatorcontrib>Loviscach, M</creatorcontrib><creatorcontrib>Stumvoll, M</creatorcontrib><creatorcontrib>Claussen, C D</creatorcontrib><creatorcontrib>Schick, F</creatorcontrib><creatorcontrib>Häring, H U</creatorcontrib><creatorcontrib>Jacob, S</creatorcontrib><title>Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans</title><title>Diabetes (New York, N.Y.)</title><addtitle>Diabetes</addtitle><description>Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity
in Humans
Oliver P. Bachmann 1 ,
Dominik B. Dahl 1 ,
Klaus Brechtel 2 ,
Jürgen Machann 2 ,
Michael Haap 1 ,
Thomas Maier 1 ,
Mattias Loviscach 1 ,
Michael Stumvoll 1 ,
Claus D. Claussen 2 ,
Fritz Schick 2 ,
Hans U. Häring 1 and
Stephan Jacob 1
1 Department of Endocrinology and Metabolism, Eberhard-Karls University, Tübingen, Germany, and
2 Department of Radiology, Eberhard-Karls University, Tübingen, Germany
Abstract
An increased intramyocellular lipid (IMCL) content, as quantified by 1 H-magnetic resonance spectroscopy ( 1 H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and
how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating
nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a
high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic
glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by 1 H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly
after 2 h, reaching a maximum of 120.8 ± 3.4% (SOL) and 164.2 ± 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 ± 5.4% of baseline
after 6 h. Over time, the GIR was strongly correlated with IMCL in TA ( r = −0.98, P ≤ 0.003) and SOL muscle ( r = −0.97, P ≤ 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after
completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased
significantly in TA muscle (to 148.0 ± 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 ± 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 ± 5.6% of baseline
( P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of
the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion
protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by
a high-fat diet, thereby underlining the physiological relevance of these observations.
Footnotes
Address correspondence and reprint requests to Dr. Hans U. Häring, Medical Clinic, Department of Endocrinology and Metabolism,
Otfried-Müller Str. 10, D-72076, Tübingen, Germany. E-mail: hans-ulrich.haering{at}med.uni-tuebingen.de
O.P.B. and D.B.D. contributed equally to the article.
Received for publication 5 March 2001 and accepted in revised form 7 August 2001.
CT, computed tomography; GIR, glucose infusion rate; IMCL, intramyocellular lipid; 1 H-MRS, 1 H-magnetic resonance spectroscopy; NEFA, nonesterified fatty acid; SOL, soleus; TA, tibialis anterior.</description><subject>Adult</subject><subject>Biological and medical sciences</subject><subject>Blood Glucose - analysis</subject><subject>Diabetes</subject><subject>Diabetes research</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diet</subject><subject>Dietary Fats - pharmacology</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Fatty acids</subject><subject>Fatty Acids, Nonesterified - blood</subject><subject>Glucose</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Injections, Intravenous</subject><subject>Insulin - blood</subject><subject>Insulin - physiology</subject><subject>Insulin resistance</subject><subject>Lipid Metabolism</subject><subject>Lipids</subject><subject>Lipids - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolism</subject><subject>Muscle, Skeletal - cytology</subject><subject>Muscle, Skeletal - metabolism</subject><subject>Musculoskeletal system</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Pathogenesis</subject><subject>Spectrum analysis</subject><subject>Type 2 diabetes</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpt0luL1DAUB_AiijuufgJBiqAg2DHXJnlcxnV3YWDBC_oW0vS0k6VNxyZdnW_gxzbjzDKMDHkoKb9_Licny15iNCeUig-1MxVECHOO5hjPCRfqUTbDiqqCEvHjcTZDCJMCCyXOsmch3CGEyjSeZmcYl0IxKmbZn8umARtDPjT5jY-juQc_TCE3vs4_Oohm3ORLt3Z1vliZrgPfQj74He03g4WumzozPpjBR_DxXzquIP8MnYku-e8urlIoTJ3z-RfwwUV37-ImT9PrqTc-PM-eNKYL8GL_Pc--fbr8urgulrdXN4uLZWG5VLEwWIiKY0kphRqwko2whDJjyoZxKwnISuCKcSNLLhlhVY0ayhlnFTZGsIqeZ293667H4ecEIerehe01jId0cS0IIVKVKsHX_8G7YRp9OpsmuGRSCooSKnaoNR1o55sh1cW24GE03eChcen3BWa8lIRjmvz8hE-jht7Zk4F3RwG7rfDv2JopBC2vlse2OGXtkN6tBZ3KuLg99nTn7TiEMEKj16Pr04trjPS2xfRDi2mONMZ622Ip9Wpfl6nqoT5k9j2VwJs9MMGarhmNty4cHMNMqRIn937nVq5d_XIjHLY7te9fN73pQg</recordid><startdate>20011101</startdate><enddate>20011101</enddate><creator>Bachmann, O P</creator><creator>Dahl, D B</creator><creator>Brechtel, K</creator><creator>Machann, J</creator><creator>Haap, M</creator><creator>Maier, T</creator><creator>Loviscach, M</creator><creator>Stumvoll, M</creator><creator>Claussen, C D</creator><creator>Schick, F</creator><creator>Häring, H U</creator><creator>Jacob, S</creator><general>American Diabetes Association</general><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>8GL</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>S0X</scope><scope>7X8</scope></search><sort><creationdate>20011101</creationdate><title>Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans</title><author>Bachmann, O P ; Dahl, D B ; Brechtel, K ; Machann, J ; Haap, M ; Maier, T ; Loviscach, M ; Stumvoll, M ; Claussen, C D ; Schick, F ; Häring, H U ; Jacob, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c589t-a177b518333ede198f7c234aa6f45c82e8b71b45a8658424bd0f35454b1aa74b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Adult</topic><topic>Biological and medical sciences</topic><topic>Blood Glucose - analysis</topic><topic>Diabetes</topic><topic>Diabetes research</topic><topic>Diabetes. Impaired glucose tolerance</topic><topic>Diet</topic><topic>Dietary Fats - pharmacology</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Fatty acids</topic><topic>Fatty Acids, Nonesterified - blood</topic><topic>Glucose</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Injections, Intravenous</topic><topic>Insulin - blood</topic><topic>Insulin - physiology</topic><topic>Insulin resistance</topic><topic>Lipid Metabolism</topic><topic>Lipids</topic><topic>Lipids - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolism</topic><topic>Muscle, Skeletal - cytology</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Musculoskeletal system</topic><topic>NMR</topic><topic>Nuclear magnetic resonance</topic><topic>Pathogenesis</topic><topic>Spectrum analysis</topic><topic>Type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bachmann, O P</creatorcontrib><creatorcontrib>Dahl, D B</creatorcontrib><creatorcontrib>Brechtel, K</creatorcontrib><creatorcontrib>Machann, J</creatorcontrib><creatorcontrib>Haap, M</creatorcontrib><creatorcontrib>Maier, T</creatorcontrib><creatorcontrib>Loviscach, M</creatorcontrib><creatorcontrib>Stumvoll, M</creatorcontrib><creatorcontrib>Claussen, C D</creatorcontrib><creatorcontrib>Schick, F</creatorcontrib><creatorcontrib>Häring, H U</creatorcontrib><creatorcontrib>Jacob, S</creatorcontrib><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>Gale In Context: High School</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bachmann, O P</au><au>Dahl, D B</au><au>Brechtel, K</au><au>Machann, J</au><au>Haap, M</au><au>Maier, T</au><au>Loviscach, M</au><au>Stumvoll, M</au><au>Claussen, C D</au><au>Schick, F</au><au>Häring, H U</au><au>Jacob, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><addtitle>Diabetes</addtitle><date>2001-11-01</date><risdate>2001</risdate><volume>50</volume><issue>11</issue><spage>2579</spage><epage>2584</epage><pages>2579-2584</pages><issn>0012-1797</issn><eissn>1939-327X</eissn><coden>DIAEAZ</coden><abstract>Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity
in Humans
Oliver P. Bachmann 1 ,
Dominik B. Dahl 1 ,
Klaus Brechtel 2 ,
Jürgen Machann 2 ,
Michael Haap 1 ,
Thomas Maier 1 ,
Mattias Loviscach 1 ,
Michael Stumvoll 1 ,
Claus D. Claussen 2 ,
Fritz Schick 2 ,
Hans U. Häring 1 and
Stephan Jacob 1
1 Department of Endocrinology and Metabolism, Eberhard-Karls University, Tübingen, Germany, and
2 Department of Radiology, Eberhard-Karls University, Tübingen, Germany
Abstract
An increased intramyocellular lipid (IMCL) content, as quantified by 1 H-magnetic resonance spectroscopy ( 1 H-MRS), is associated with reduced insulin sensitivity. At present, it is unclear which factors determine IMCL formation and
how rapidly IMCL accumulation can be induced. We therefore studied the impact of hyperinsulinemia and elevated circulating
nonesterified fatty acid (NEFA) levels on IMCL formation and insulin sensitivity. We further evaluated the influence of a
high-fat diet on IMCL storage. In the infusion protocol, 12 healthy male subjects underwent a 6-h hyperinsulinemic-euglycemic
glucose clamp with concomitant infusion of Intralipid plus heparin. IMCL was quantified by 1 H-MRS in soleus (SOL) and tibialis anterior (TA) muscle at baseline and then every hour. IMCL levels started to increase significantly
after 2 h, reaching a maximum of 120.8 ± 3.4% (SOL) and 164.2 ± 13.8% (TA) of baseline after 6 h (both P < 0.05). In parallel, the glucose infusion rate (GIR) decreased progressively, reaching a minimum of 60.4 ± 5.4% of baseline
after 6 h. Over time, the GIR was strongly correlated with IMCL in TA ( r = −0.98, P ≤ 0.003) and SOL muscle ( r = −0.97, P ≤ 0.005). In the diet protocol, 12 male subjects ingested both a high-fat and low-fat diet for 3 days each. Before and after
completion of each diet, IMCL levels and insulin sensitivity were assessed. After the high-fat diet, IMCL levels increased
significantly in TA muscle (to 148.0 ± 16.9% of baseline; P = 0.005), but not in SOL muscle (to 114.4 ± 8.2% of baseline; NS). Insulin sensitivity decreased to 83.3 ± 5.6% of baseline
( P = 0.033). There were no significant changes in insulin sensitivity or IMCL levels after the low-fat diet. The effects of
the high-fat diet showed greater interindividual variation than those of the infusion protocol. The data from the lipid infusion
protocol suggest a functional relationship between IMCL levels and insulin sensitivity. Similar effects could be induced by
a high-fat diet, thereby underlining the physiological relevance of these observations.
Footnotes
Address correspondence and reprint requests to Dr. Hans U. Häring, Medical Clinic, Department of Endocrinology and Metabolism,
Otfried-Müller Str. 10, D-72076, Tübingen, Germany. E-mail: hans-ulrich.haering{at}med.uni-tuebingen.de
O.P.B. and D.B.D. contributed equally to the article.
Received for publication 5 March 2001 and accepted in revised form 7 August 2001.
CT, computed tomography; GIR, glucose infusion rate; IMCL, intramyocellular lipid; 1 H-MRS, 1 H-magnetic resonance spectroscopy; NEFA, nonesterified fatty acid; SOL, soleus; TA, tibialis anterior.</abstract><cop>Alexandria, VA</cop><pub>American Diabetes Association</pub><pmid>11679437</pmid><doi>10.2337/diabetes.50.11.2579</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0012-1797 |
ispartof | Diabetes (New York, N.Y.), 2001-11, Vol.50 (11), p.2579-2584 |
issn | 0012-1797 1939-327X |
language | eng |
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source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
subjects | Adult Biological and medical sciences Blood Glucose - analysis Diabetes Diabetes research Diabetes. Impaired glucose tolerance Diet Dietary Fats - pharmacology Endocrine pancreas. Apud cells (diseases) Endocrinopathies Etiopathogenesis. Screening. Investigations. Target tissue resistance Fatty acids Fatty Acids, Nonesterified - blood Glucose Health aspects Humans Injections, Intravenous Insulin - blood Insulin - physiology Insulin resistance Lipid Metabolism Lipids Lipids - pharmacology Male Medical sciences Metabolism Muscle, Skeletal - cytology Muscle, Skeletal - metabolism Musculoskeletal system NMR Nuclear magnetic resonance Pathogenesis Spectrum analysis Type 2 diabetes |
title | Effects of Intravenous and Dietary Lipid Challenge on Intramyocellular Lipid Content and the Relation With Insulin Sensitivity in Humans |
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