Linked Life Data

12213853

Source:http://linkedlifedata.com/resource/pubmed/id/12213853

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2002-9-5
pubmed:abstractText
Insulin resistance is characteristic of many patients with polycystic ovary syndrome (PCOS). Several studies have suggested that a decrease in insulin receptor (IR) autophosphorylation is a significant component of this resistance. In this study, we have used a highly sensitive ELISA to measure IR tyrosine phosphorylation in fibroblasts from patients with PCOS and healthy control women. After the stimulation of intact fibroblasts with insulin, IR tyrosine phosphorylation in cells from the PCOS patients was decreased by approximately 40% when compared with controls. However, when IR were first immunocaptured from fibroblasts and then stimulated with insulin, neither basal nor insulin-stimulated IR autophosphorylation was different between the two groups, suggesting that a factor independent of the IR was involved. To examine the role of increased serine kinase activity in decreased IR autophosphorylation in PCOS, fibroblasts from PCOS patients were pretreated with inhibitors of serine kinases before insulin stimulation. Pretreatment with H7, a nonspecific protein kinase inhibitor, completely reversed the decrease in insulin-stimulated IR autophosphorylation. Pretreatment with H89, an inhibitor of protein kinase A, partially reversed this function, whereas pretreatment with Gö6983, an inhibitor of protein kinase C, was without effect. We next studied the effects of two small molecule activators of the IR tyrosine kinase: TLK16998 and Merck L7. Both TLK16998 and Merck L7 were able to reverse the impaired insulin-stimulated IR autophosphorylation. In summary, a factor(s) extrinsic to the IR cause impaired IR signaling in fibroblasts from patients with PCOS. Reversal of the impaired IR signaling by inhibitors of serine kinase activity suggests that serine kinase-mediated pathways may be involved in the insulin resistance. Moreover, the observation that TLK16998 and Merck L7 improved IR tyrosine phosphorylation in fibroblasts from patients with PCOS suggests that specific pharmacological therapies might be developed to treat the insulin resistance in PCOS.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-972X
pubmed:author
pubmed:issnType
Print
pubmed:volume
87
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4088-93
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Decreased insulin receptor (IR) autophosphorylation in fibroblasts from patients with PCOS: effects of serine kinase inhibitors and IR activators.
pubmed:affiliation
University of California at San Francisco, Mount Zion Medical Center, San Francisco, California 94143, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't