Linked Life Data

15561934

Source:http://linkedlifedata.com/resource/pubmed/id/15561934

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2004-11-24
pubmed:abstractText
Protein tyrosine phosphatase-1B (PTP-1B) plays an important role in regulation of insulin signal transduction, and modulation of PTP-1B expression seems to have a profound effect on insulin sensitivity and diet-induced weight gain. The molecular link between PTP-1B expression and metabolic dyslipidemia, a major complication of insulin resistance, was investigated in the present study using PTP-1B knockout mice as well as overexpression and suppression of PTP-1B. Chronic fructose feeding resulted in a significant increase in plasma VLDL in wild-type mice but not in PTP-1B knockout mice. Lipoprotein profile analysis of plasma from PTP-1B knockout mice revealed a significant reduction in apolipoprotein B (apoB100) lipoproteins, associated with reduced hepatic apoB100 secretion from isolated primary hepatocytes. In addition, treatment of cultured hepatoma cells with PTP-1B siRNA reduced PTP-1B mass by an average of 41% and was associated with a 53% decrease in secretion of metabolically labeled apoB100. Conversely, adenoviral-mediated overexpression of PTP-1B in HepG2 cells downregulated the phosphorylation of insulin receptor and insulin receptor substrate-1 and caused increases in cellular and secreted apoB100 as a result of increased intracellular apoB100 stability. Collectively, these findings suggest that PTP-1B expression level is a key determinant of hepatic lipoprotein secretion, and its overexpression in the liver can be sufficient to induce VLDL overproduction and the transition to a metabolic dyslipidemic state.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3057-66
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15561934-Animals, pubmed-meshheading:15561934-Apolipoprotein B-100, pubmed-meshheading:15561934-Apolipoproteins B, pubmed-meshheading:15561934-Cell Line, pubmed-meshheading:15561934-Cell Line, Tumor, pubmed-meshheading:15561934-Cholesterol, pubmed-meshheading:15561934-Hepatocytes, pubmed-meshheading:15561934-Humans, pubmed-meshheading:15561934-Liver, pubmed-meshheading:15561934-Mice, pubmed-meshheading:15561934-Mice, Knockout, pubmed-meshheading:15561934-Protein Tyrosine Phosphatase, Non-Receptor Type 1, pubmed-meshheading:15561934-Protein Tyrosine Phosphatases, pubmed-meshheading:15561934-RNA, Antisense, pubmed-meshheading:15561934-RNA, Small Interfering, pubmed-meshheading:15561934-Reference Values, pubmed-meshheading:15561934-Transfection, pubmed-meshheading:15561934-Triglycerides
pubmed:year
2004
pubmed:articleTitle
Hepatic PTP-1B expression regulates the assembly and secretion of apolipoprotein B-containing lipoproteins: evidence from protein tyrosine phosphatase-1B overexpression, knockout, and RNAi studies.
pubmed:affiliation
Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't