Mouse and human resistins impair glucose transport in primary mouse cardiomyocytes, and oligomerization is required for this biological action

Christophe Graveleau, Vlad G. Zaha, Arash Mohajer, Ronadip R. Banerjee, Nicole Dudley-Rucker, Claire M. Steppan, Michael W. Rajala, Philipp E. Scherer, Rexford S. Ahima, Mitchell A. Lazar, E. Dale Abel

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

The adipocytokine resistin impairs glucose tolerance and insulin sensitivity in rodents. Here, we examined the effect of resistin on glucose uptake in isolated adult mouse cardiomyocytes. Murine resistin reduced insulin-stimulated glucose uptake, establishing the heart as a resistin target tissue. Notably, human resistin also impaired insulin action in mouse cardiomyocytes, providing the first evidence that human and mouse resistin homologs have similar functions. Resistin is a cysteinerich molecule that circulates as a multimer of a dimeric form dependent upon a single intermolecular disulfide bond, which, in the mouse, involves Cys26; mutation of this residue to alanine (C26A) produces a monomeric molecule that appears to be bioactive in the liver. Remarkably, unlike native resistin, monomeric C26A resistin had no effect on basal or insulin-stimulated glucose uptake in mouse cardiomyocytes. Resistin impairs glucose uptake in cardiomyocytes by mechanisms that involve altered vesicle trafficking. Thus, in cardiomyocytes, both mouse and human resistins directly impair glucose transport; and in contrast to effects on the liver, these actions of resistin require oligomerization.

Original languageEnglish (US)
Pages (from-to)31679-31685
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number36
DOIs
StatePublished - Sep 9 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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