Document Detail


Changes in phosphatidylcholine fatty acid composition are associated with altered skeletal muscle insulin responsiveness in normal man.
MedLine Citation:
PMID:  10690951     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The fatty acid composition of skeletal muscle cell membrane phospholipids (PLs) is known to influence insulin responsiveness in man. We have recently shown that the fatty acid composition of phosphatidylcholine (PC), and not phosphatidylethanolamine (PE), from skeletal muscle membranes is of particular importance in this relationship. Efforts to alter the PL fatty acid composition in animal models have demonstrated induction of insulin resistance. However, it has been more difficult to determine if changes in insulin sensitivity are associated with changes in the skeletal muscle membrane fatty acid composition of PL in man. Using nicotinic acid (NA), an agent known to induce insulin resistance in man, 9 normal subjects were studied before and after treatment for 1 month. Skeletal muscle membrane fatty acid composition of PC and PE from biopsies of vastus lateralis was correlated with insulin responsiveness using a 3-step hyperinsulinemic-euglycemic clamp. Treatment with NA was associated with a 25% increase in the half-maximal insulin concentration ([ED50] 52.0 +/- 7.5 to 64.6 +/- 9.0 microU/mL, P < .05), consistent with decreased peripheral insulin sensitivity. Significant changes in the fatty acid composition of PC, but not PE, were also observed after NA administration. An increase in the percentage of 16:0 (21% +/- 0.3% to 21.7% +/- 0.4%, P < .05) and decreases in 18:0 (6.2% +/- 0.5% to 5.1% +/- 0.4%, P = .01), long-chain n-3 fatty acids (1.7% +/- 0.2% to 1.4% +/- 0.1%, P < .01), and total polyunsaturated fatty acids ([PUFAs] 8.7% +/- 0.8% to 8.0% +/- 0.8%, P < .05) are consistent with a decrease in fatty acid length and unsaturation in PC following NA administration. The change in ED50 was significantly correlated with the change in PUFAs (r = -.65, P < .05). These studies suggest that the induction of insulin resistance with NA is associated with changes in the fatty acid composition of PC in man.
Authors:
J N Clore; P A Harris; J Li; A Azzam; R Gill; W Zuelzer; W B Rizzo; W G Blackard
Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Metabolism: clinical and experimental     Volume:  49     ISSN:  0026-0495     ISO Abbreviation:  Metab. Clin. Exp.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-06     Completed Date:  2000-03-06     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0375267     Medline TA:  Metabolism     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  232-8     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Virginia Commonwealth University, Richmond 23298, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Blood Glucose / metabolism
Carbohydrate Metabolism
Cell Membrane / metabolism
Fatty Acids / metabolism*
Female
Glucose Clamp Technique
Glycerol / blood
Humans
Insulin / blood
Insulin Resistance / physiology*
Lipid Metabolism
Male
Muscle Fibers, Skeletal / physiology
Muscle, Skeletal / cytology,  metabolism*
Niacin / pharmacology*
Oxidation-Reduction
Phosphatidylcholines / metabolism*
Phosphatidylethanolamines / metabolism
Grant Support
ID/Acronym/Agency:
MO1 RR00065/RR/NCRR NIH HHS; R01 DK18903/DK/NIDDK NIH HHS; R01 DK43013/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Fatty Acids; 0/Phosphatidylcholines; 0/Phosphatidylethanolamines; 11061-68-0/Insulin; 56-81-5/Glycerol; 59-67-6/Niacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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