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Science Forum Index » Life Extension Forum » Downregulation of pyruvate dehydrogenase complex in diabetic
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| kofi |
 Posted: Tue Jan 13, 2004 1:41 pm |
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Proc Natl Acad Sci U S A. 2002 Aug 6;99(16):10587-92. Epub 2002 Jul 29.
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Coordinated patterns of gene expression for substrate and energy
metabolism in skeletal muscle of diabetic mice.
Yechoor VK, Patti ME, Saccone R, Kahn CR.
Joslin Diabetes Center and Department of Medicine, Harvard Medical
School, One Joslin Place, Boston, MA 02215, USA.
Metabolic abnormalities underlying diabetes are primarily the result
of the lack of adequate insulin action and the associated changes in
protein phosphorylation and gene expression. To define the full set of
alterations in gene expression in skeletal muscle caused by diabetes and
the loss of insulin action, we have used Affymetrix oligonucleotide
microarrays and streptozotocin-diabetic mice. Of the genes studied, 235
were identified as changed in diabetes, with 129 genes up-regulated and
106 down-regulated. Analysis revealed a coordinated regulation at key
steps in glucose and lipid metabolism, mitochondrial electron transport,
transcriptional regulation, and protein trafficking. mRNAs for all of
the enzymes of the fatty acid beta-oxidation pathway were increased,
whereas those for GLUT4, hexokinase II, the E1 component of the pyruvate
dehydrogenase complex, and subunits of all four complexes of the
mitochondrial electron transport chain were all coordinately
down-regulated. Only about half of the alterations in gene expression in
diabetic mice could be corrected toward normal after 3 days of insulin
treatment and euglycemia. These data point to as of yet undefined
mechanisms for highly coordinated regulation of gene expression by
insulin and potential new targets for therapy of diabetes mellitus.
PMID: 12149437 [PubMed - indexed for MEDLINE] |
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