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
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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