Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/24832
Share/Export:
logo share SHARE logo core CORE BASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Title

Developmental switch from prolonged insulin action to increased insulin sensitivity in protein tyrosine phosphatase 1B-deficient hepatocytes

AuthorsGonzález-Rodríguez, Águeda; Escribano, Óscar; Benito, Manuel; Rondinone, Cristina M.; Valverde, Ángela M.
Issue DateFeb-2007
PublisherEndocrine Society
CitationEndocrinology 148(2): 594-608 (2007)
AbstractProtein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. The purpose of this study was to evaluate the differences in insulin sensitivity between neonate and adult hepatocytes lacking PTP1B. Immortalized neonatal hepatocytes and primary neonatal and adult hepatocytes have been generated from PTP1B(-/-) and wild-type mice. PTP1B deficiency in immortalized neonatal hepatocytes prolonged insulin-induced tyrosine phosphorylation of the insulin receptor (IR) and IR substrates (IRS) -1, -2 compared with wild-type control cells. Endogenous IR and IRS-2 were down-regulated, whereas IRS-1 was up-regulated in PTP1B(-/-) neonatal hepatocytes and livers of PTP1B(-/-) neonates. Insulin-induced activation of phosphatidylinositol 3-kinase/Akt pathway was prolonged in PTP1B(-/-) immortalized neonatal hepatocytes. However, insulin sensitivity was comparable to wild-type hepatocytes. Rescue of PTP1B in deficient cells suppressed the prolonged insulin signaling, whereas RNA interference in wild-type cells promoted prolonged signaling. In primary neonatal PTP1B(-/-) hepatocytes, insulin prolonged the inhibition of gluconeogenic mRNAs, but the sensitivity to this inhibition was similar to wild-type cells. By contrast, in adult PTP1B-deficient livers, p85alpha was down-regulated compared with the wild type. Moreover, primary hepatocytes from adult PTP1B(-/-) mice displayed enhanced Akt phosphorylation and a more pronounced inhibition of gluconeogenic mRNAs than wild-type cells. Hepatic insulin sensitivity due to PTP1B deficiency is acquired through postnatal development. Thus, changes in IR and IRS-2 expression and in the balance between regulatory and catalytic subunits of phosphatidylinositol 3-kinase are necessary to achieve insulin sensitization in adult PTP1B(-/-) hepatocytes.
Description15 pages, 10 figures.
Publisher version (URL)http://dx.doi.org/10.1210/en.2006-0644
URIhttp://hdl.handle.net/10261/24832
DOI10.1210/en.2006-0644
ISSN0013-7227
Appears in Collections:(IIBM) Artículos




Files in This Item:
File Description SizeFormat
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work

SCOPUSTM   
Citations

43
checked on May 23, 2022

WEB OF SCIENCETM
Citations

37
checked on May 28, 2022

Page view(s)

386
checked on May 28, 2022

Download(s)

106
checked on May 28, 2022

Google ScholarTM

Check

Altmetric

Dimensions


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.