Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content.

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Ressource 1Télécharger: Serval_PostPrint_2010_Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes.pdf (3318.49 [Ko])
Etat: Serval
Version: Author's accepted manuscript
ID Serval
serval:BIB_EB15303EFDD1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Insulin resistance is associated with higher intramyocellular triglycerides in type I but not type II myocytes concomitant with higher ceramide content.
Périodique
Diabetes
Auteur(s)
Coen P.M., Dubé J.J., Amati F., Stefanovic-Racic M., Ferrell R.E., Toledo F.G., Goodpaster B.H.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Statut éditorial
Publié
Date de publication
2010
Volume
59
Numéro
1
Pages
80-88
Langue
anglais
Notes
Publication types: Journal Article
Résumé
OBJECTIVE: We tested the primary hypotheses that sphingolipid and diacylglycerol (DAG) content is higher within insulin-resistant muscle and that the association between intramyocellular triglycerides (IMTG) and insulin resistance is muscle fiber type specific.
RESEARCH DESIGN AND METHODS: A nested case-control analysis was conducted in 22 obese (BMI >30 kg/m(2)) women who were classified as insulin-resistant (IR; n = 12) or insulin-sensitive (IS; n = 10), determined by hyperinsulinemic-euglycemic clamp (>30% greater in IS compared with IR, P < 0.01). Sphingolipid and DAG content was determined by high-performance liquid chromatography-tandem mass spectrometry. Fiber type-specific IMTG content was histologically determined. Gene expression was determined by quantitative PCR.
RESULTS: Total (555 +/- 53 vs. 293 +/- 54 pmol/mg protein, P = 0.004), saturated (361 +/- 29 vs. 179 +/- 34 pmol/mg protein, P = 0.001), and unsaturated (198 +/- 29 vs. 114 +/- 21 pmol/mg protein, P = 0.034) ceramides were higher in IR compared with IS. DAG concentrations, however, were similar. IMTG content within type I myocytes, but not type II myocytes, was higher in IR compared with IS subjects (P = 0.005). Insulin sensitivity was negatively correlated with IMTG within type I myocytes (R = -0.51, P = 0.026), but not with IMTG within type II myocytes. The proportion of type I myocytes was lower (41 vs. 59%, P < 0.01) in IR subjects. Several genes involved in lipid droplet and fatty acid metabolism were differentially expressed in IR compared with IS subjects.
CONCLUSIONS: Human skeletal muscle insulin resistance is related to greater IMTG content in type I but not type II myocytes, to greater ceramide content, and to alterations in gene expression associated with lipid metabolism.
Mots-clé
Actins/genetics, Biopsy, Body Composition, Ceramides/metabolism, Diglycerides/metabolism, Fatty Acids, Nonesterified/blood, Female, Gene Expression, Glyceraldehyde-3-Phosphate Dehydrogenases/genetics, Humans, Hypoxanthine Phosphoribosyltransferase/genetics, Insulin Resistance/physiology, Muscle Cells/metabolism, Muscle Cells/physiology, Muscle, Skeletal/physiology, Muscle, Skeletal/physiopathology, Polymerase Chain Reaction, RNA/genetics, Sphingolipids/metabolism, Triglycerides/metabolism, beta 2-Microglobulin/genetics
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/03/2011 10:34
Dernière modification de la notice
09/05/2019 2:57
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