English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/152494
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Increased insulin sensitivity in IGF-I receptor-deficient brown adipocytes

AuthorsMur, Cecilia; Valverde, Ángela M.; Kahn, C. Ronald; Benito, Manuel
Issue Date2002
PublisherAmerican Diabetes Association
CitationDiabetes 51(3): 743-754 (2002)
AbstractImmortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR-/-), as well as from fetuses of wild-type mice (IGF-IR+/+). These cell lines maintained the expression of adipogenic-and thermogenic-differentiation markers and show a multilocular fat droplets phenotype. IGF-IR-/- brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. Insulin-induced tyrosine autophosphorylation of the IR β-chain was augmented in IGF-IR-deficient cells. Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR-/- brown adipocytes, although IRS-1 protein content was reduced. In contrast, tyrosine phosphorylation of IRS-2 decreased in IGF-IR-deficient cells; its protein content was unchanged as compared with wild-type cells. Down-stream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR-/- brown adipocyte cell line. However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR-deficient brown adipocytes. These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. Data presented here provide strong evidence that IGF-IR-deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin.
Identifiersdoi: 10.2337/diabetes.51.3.743
issn: 0012-1797
e-issn: 1939-327X
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

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