Linked Life Data

19501568

Source:http://linkedlifedata.com/resource/pubmed/id/19501568

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-7-1
pubmed:abstractText
HIV-protease inhibitors (PIs) markedly decreased mortality of HIV-infected patients. However, their use has been associated with occurence of metabolic abnormalities the causes of which are not well understood. We report here that lopinavir, one of the most prescribed PI, dose-dependently co-induced insulin resistance and ER stress in human adipocytes obtained from differentiation of precursor cells. Insulin resistance was subsequent to IRS1 phosphorylation defects and resulted in a concentration-dependent decrease of glucose uptake. The major ER stress pathway involved was the phosphorylation of eIF2-alpha. Salubrinal, a selective eIF2-alpha dephosphorylation inhibitor, induced insulin resistance by targeting IRS1 phosphorylation at serine 312 and acted synergistically with LPV when both drugs were used in combination. This study points out the key role of eIF2-alpha phosphorylation in the development of PI-associated insulin resistance and ER stress. Thus, this protein represents a promising therapeutic target for development of new PIs devoid of adverse metabolic effects.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
14
pubmed:volume
386
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
96-100
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Lopinavir co-induces insulin resistance and ER stress in human adipocytes.
pubmed:affiliation
Institute of Biology Development and Cancer, University of Nice Sophia-Antipolis, CNRS, 28 Avenue de Valombrose, 06107 NICE Cedex2, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't