Horm Metab Res 2006; 38(6): 391-396
DOI: 10.1055/s-2006-944531
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Altered GLUT4 Translocation in Skeletal Muscle of 12/15-Lipoxygenase Knockout Mice

S.  Vahsen1 , K.  Rakowski1 , D.  Ledwig1 , D.  Dietze-Schroeder1 , J.  Swifka1 , S.  Sasson2 , J.  Eckel1
  • 1Institute of Clinical Biochemistry and Pathobiochemistry, German Diabetes Center, Düsseldorf, Germany
  • 2Hebrew University of Jerusalem, Jerusalem, Israel
Further Information

Publication History

Received 31 October 2005

Accepted after revision 9 January 2006

Publication Date:
06 July 2006 (online)

Abstract

We have recently shown that 12(S)-hydroxyeicosatetraenoic acid plays a role in the organization of actin microfilaments in rat cardiomyocytes, and that inhibition of 12-lipoxygenase abrogates insulin-stimulated GLUT4 translocation in these cells. In the present study, we used mice that were null for the leukocyte 12/15-lipoxygenase to explore the implications of this enzyme for insulin action under in vivo conditions. Insulin induced a profound reduction in blood glucose in both control and knockout mice. However, significantly higher serum insulin levels were observed in these animals. GLUT4 expression in heart and skeletal muscle was unaffected in KO mice. Insulin-regulated serine phosphorylation of Akt and GSK3α and GSK3β was unaltered in heart and skeletal muscle of knockout mice, suggesting unaltered insulin signaling. Fractionation of hind limb muscles showed that insulin had induced a prominent translocation of GLUT4 to skeletal muscle plasma membranes in control mice. However, this response was largely reduced in knockout animals. Our data show that the lack of leukocyte 12/15-lipoxygenase does not lead to the development of an insulin-resistant phenotype. However, perturbation of GLUT4 translocation in skeletal muscle of knockout mice may indicate latent insulin resistance, and supports our hypothesis that eicosanoids are involved in insulin-mediated regulation of muscle glucose transport.

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Prof. Dr. Jürgen Eckel

German Diabetes Center

Auf'm Hennekamp 65 · 40225 Düsseldorf · Germany ·

Phone: +49 (211) 338 25 61

Fax: +49 (211) 338 26 97

Email: eckel@uni-duesseldorf.de