Linked Life Data

17554339

Source:http://linkedlifedata.com/resource/pubmed/id/17554339

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7147
pubmed:dateCreated
2007-6-21
pubmed:abstractText
Type 2 diabetes mellitus, a disease with significant effects on the health and economy of Western societies, involves disturbances in both lipid and carbohydrate metabolism. In the insulin-resistant or diabetic state, the liver is unresponsive to the actions of insulin with regard to the suppression of glucose output but continues to produce large amounts of lipid, the latter mimicking the fed, insulin-replete condition. The disordered distribution of lipids contributes to the cardiovascular disease that is the greatest cause of mortality of type 2 diabetes mellitus. Yet the precise signal transduction pathways by which insulin regulates hepatic lipid synthesis and degradation remain largely unknown. Here we describe a mechanism by which insulin, through the intermediary protein kinase Akt2/protein kinase B (PKB)-beta, elicits the phosphorylation and inhibition of the transcriptional coactivator peroxisome proliferator-activated receptor-coactivator 1alpha (PGC-1alpha), a global regulator of hepatic metabolism during fasting. Phosphorylation prevents the recruitment of PGC-1alpha to the cognate promoters, impairing its ability to promote gluconeogenesis and fatty acid oxidation. These results define a mechanism by which insulin controls lipid catabolism in the liver and suggest a novel site for therapy in type 2 diabetes mellitus.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
21
pubmed:volume
447
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1012-6
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Akt/PKB regulates hepatic metabolism by directly inhibiting PGC-1alpha transcription coactivator.
pubmed:affiliation
Institute for Diabetes, Obesity and Metabolism, Cox Institute, University of Pennsylvania School of Medicine and the Howard Hughes Medical Institute, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural