Please use this identifier to cite or link to this item: http://hdl.handle.net/10316/21212
Title: Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin
Authors: Rosa, S. C. 
Rufino, A. T. 
Judas, F. 
Tenreiro, C. 
Lopes, M. C. 
Mendes, A. F. 
Keywords: Anabolic gene expression; Glucose transport; Human chondrocyte; Insulin; Insulin receptor; Insulin-like growth factor receptor; Osteoarthritis
Issue Date: Jun-2011
Publisher: Elsevier
Citation: ROSA, S. C. [at al.] - Expression and function of the insulin receptor in normal and osteoarthritic human chondrocytes: modulation of anabolic gene expression, glucose transport and GLUT-1 content by insulin. "Osteoarthritis and Cartilage". ISSN 1063-4584. 19:6 (2011) 719-727
Serial title, monograph or event: Osteoarthritis and Cartilage
Volume: 19
Issue: 6
Abstract: Objective Chondrocytes respond to insulin, but the presence and role of the specific high affinity insulin receptor (InsR) has never been demonstrated. This study determined whether human chondrocytes express the InsR and compared its abundance and function in normal and osteoarthritis (OA) human chondrocytes. Design Cartilage sections were immunostained for detection of the InsR. Non-proliferating chondrocyte cultures from normal and OA human cartilage were treated with 1 nM or 10 nM insulin for various periods. InsR, insulin-like growth factor receptor (IGFR), aggrecan and collagen II mRNA levels were assessed by real time RT-PCR. InsR, glucose transporter (GLUT)-1, phospho-InsRbeta and phospho-Akt were evaluated by western blot and immunofluorescence. Glucose transport was measured as the uptake of [3H]-2-Deoxy-d-Glucose (2-DG). Results Chondrocytes staining positively for the InsR were scattered throughout the articular cartilage. The mRNA and protein levels of the InsR in OA chondrocytes were approximately 33% and 45%, respectively, of those found in normal chondrocytes. Insulin induced the phosphorylation of the InsRbeta subunit. Akt phosphorylation and 2-DG uptake increased more intensely in normal than OA chondrocytes. Collagen II mRNA expression increased similarly in normal and OA chondrocytes while aggrecan expression remained unchanged. The Phosphoinositol-3 Kinase (PI3K)/Akt pathway was required for both basal and insulin-induced collagen II expression. Conclusions Human chondrocytes express functional InsR that respond to physiologic insulin concentrations. The InsR seems to be more abundant in normal than in OA chondrocytes, but these still respond to physiologic insulin concentrations, although some responses are impaired while others appear fully activated. Understanding the mechanisms that regulate the expression and function of the InsR in normal and OA chondrocytes can disclose new targets for the development of innovative therapies for OA.
URI: http://hdl.handle.net/10316/21212
ISSN: 1063-4584
DOI: 10.1016/j.joca.2011.02.004
Rights: openAccess
Appears in Collections:FFUC- Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
I&D CMUC - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
Expression and function of the insulin receptor.pdf315.15 kBAdobe PDFView/Open
Show full item record

SCOPUSTM   
Citations

31
checked on Feb 18, 2020

WEB OF SCIENCETM
Citations

32
checked on May 29, 2020

Page view(s) 20

604
checked on May 28, 2020

Download(s)

156
checked on May 28, 2020

Google ScholarTM

Check

Altmetric

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.