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Horm Metab Res 2007; 39(8): 575-581
DOI: 10.1055/s-2007-985132
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Discoidin Domain Receptor 2 Impairs Insulin-stimulated Insulin Receptor Substrate-1 Tyrosine Phosphorylation and Glucose Uptake in 3T3-L1 Adipocytes

H. Zurakowski 1 , A. Gagnon 1 , A. Landry 1 , M. D. Layne 2 , A. Sorisky 1
  • 1Departments of Medicine and of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa Health Research Institute, Ottawa, ON K1Y 4E9 Canada
  • 2Pulmonary Division, Brigham and Women's Hospital, Harvard Medical School, Boston, USA
Further Information

Publication History

received 27.11.2006

accepted 27.02.2007

Publication Date:
21 August 2007 (online)

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Abstract

Differentiation of preadipocytes into functional adipocytes depends on early proliferative events (mitotic clonal expansion) and extracellular matrix interactions. We report that discoidin domain receptor (DDR) 2, a novel adhesion receptor, is expressed in 3T3-L1 preadipocytes and is downregulated during the early phase of adipogenesis. DDR2 overexpression (DDR2-L1 preadipocytes) reduced subconfluent proliferation by 56% (p<0.001) and insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS)-1 by 34% (p<0.05). The mitotic clonal expansion phase of differentiating confluent DDR2-L1 preadipocytes was impaired by ∼25% (p<0.05). Although induction of peroxisome proliferator-activated receptor γ, fatty acid synthase, and adiponectin was not altered, the resulting adipocytes were 55% larger (p<0.05), and contained 66% more triacylglycerol (p<0.01). The induction of CCAAT/enhancer binding protein α was reduced by 37% (p<0.05), correlating with a similar reduction in insulin-stimulated IRS-1 tyrosine phosphorylation and glucose transport in DDR2-L1 adipocytes (decreases of 22% and 27%, respectively; p<0.05 for both). Our data show that DDR2 is expressed in adipose cells and that its overexpression leads to insulin resistance.

Key words

Preadipocyte - differentiation - collagen - extracellular matrix - proliferation - insulin resistance

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Correspondence

Dr. A. Sorisky

Ottawa Health Research Institute

725 Parkdale Avenue

Ottawa ON K1Y 4E9

Canada

Phone: +1/613/798 55 55 175 72

Fax: +1/613/761 50 36

Email: asorisky@ohri.ca

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