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

doi:10.1074/jbc.M504008200

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

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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, …

The Journal of biological chemistry, Vol.280(36), pp.31679-31685

09/09/2005

DOI: 10.1074/jbc.M504008200

PMID: 15983036

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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 cysteine-rich 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.

Phosphorylation

Insulin - physiology

Humans

Hormones, Ectopic - metabolism

Male

Protein Transport - physiology

Exocytosis - physiology

Biological Transport, Active - physiology

Muscle Proteins - metabolism

Dimerization

Monosaccharide Transport Proteins - metabolism

Protein-Serine-Threonine Kinases - metabolism

Resistin

Proto-Oncogene Proteins - metabolism

Glucose Transporter Type 4

Mice, Inbred C57BL

Hormones, Ectopic - physiology

Glucose - antagonists & inhibitors

Proto-Oncogene Proteins c-akt

Animals

Hormones, Ectopic - genetics

Glucose - metabolism

Myocytes, Cardiac - metabolism

Mice

Mutation

Transferrin - metabolism

Details

Title: Subtitle: Mouse and human resistins impair glucose transport in primary mouse cardiomyocytes, and oligomerization is required for this biological action
Creators: Christophe Graveleau - Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, Utah 84112, USA
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
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.280(36), pp.31679-31685
DOI: 10.1074/jbc.M504008200
PMID: 15983036
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: T32-GM07288 / NIGMS NIH HHS DK58073 / NIDDK NIH HHS DK55758 / NIDDK NIH HHS DK49780 / NIDDK NIH HHS R01 DK092065 / NIDDK NIH HHS DK49210 / NIDDK NIH HHS
Language: English
Date published: 09/09/2005
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024541402771

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