Paradoxical Changes in Muscle Gene Expression in Insulin-Resistant Subjects After Sustained Reduction in Plasma Free Fatty Acid Concentration
Adult
Male
0301 basic medicine
Gene Expression Profiling
Muscle Proteins
Free Radical Scavengers
Fatty Acids, Nonesterified
Middle Aged
3. Good health
03 medical and health sciences
Gene Expression Regulation
Pyrazines
Humans
Insulin
Female
RNA, Messenger
Insulin Resistance
Muscle, Skeletal
Hypolipidemic Agents
DOI:
10.2337/db06-0840
Publication Date:
2007-02-27T18:14:43Z
AUTHORS (6)
ABSTRACT
Lipid oversupply plays a role in developing insulin resistance skeletal muscle, decreasing expression of nuclear-encoded mitochondrial genes, and increasing extracellular matrix remodeling. To determine if decrease plasma lipid content reverses these abnormalities, insulin-resistant subjects with family history type 2 diabetes had euglycemic clamps muscle biopsies before after acipimox treatment to suppress free fatty acids. Free acids fell from 0.584 +/- 0.041 0.252 0.053 mmol/l (P < 0.001) glucose disposal increased 5.28 0.46 6.31 0.55 mg . kg(-1) min(-1) 0.05) acipimox; intramuscular acyl CoA decreased 10.3 1.9 4.54 0.82 pmol/mg 0.01). Paradoxically, PGC-1-and genes acipimox, collagens I III alpha-subunits (82- 21-fold increase, respectively, P 0.05), connective tissue growth factor (2.5-fold 0.001), transforming factor-beta1 (2.95-fold 0.05). Therefore, reduction supply does not completely reverse the molecular changes associated muscle. Changes do always correlate sensitivity.
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