Sarcoglycan Complex: IMPLICATIONS FOR METABOLIC DEFECTS IN MUSCULAR DYSTROPHIES

Séverine Groh; Haihong Zong; Matthew M Goddeeris; Connie S Lebakken; David Venzke; Jeffrey E Pessin; Kevin P Campbell

doi:10.1074/jbc.C109.010728

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Sarcoglycan Complex: IMPLICATIONS FOR METABOLIC DEFECTS IN MUSCULAR DYSTROPHIES

Journal article

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Sarcoglycan Complex: IMPLICATIONS FOR METABOLIC DEFECTS IN MUSCULAR DYSTROPHIES

Séverine Groh, Haihong Zong, Matthew M Goddeeris, Connie S Lebakken, David Venzke, Jeffrey E Pessin and Kevin P Campbell

The Journal of biological chemistry, Vol.284(29), pp.19178-19182

07/17/2009

DOI: 10.1074/jbc.C109.010728

PMCID: PMC2740540

PMID: 19494113

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Abstract

The sarcoglycans are known as an integral subcomplex of the dystrophin glycoprotein complex, the function of which is best characterized in skeletal muscle in relation to muscular dystrophies. Here we demonstrate that the white adipocytes, which share a common precursor with the myocytes, express a cell-specific sarcoglycan complex containing β-, δ-, and ϵ-sarcoglycan. In addition, the adipose sarcoglycan complex associates with sarcospan and laminin binding dystroglycan. Using multiple sarcoglycan null mouse models, we show that loss of α-sarcoglycan has no consequence on the expression of the adipocyte sarcoglycan complex. However, loss of β- or δ-sarcoglycan leads to a concomitant loss of the sarcoglycan complex as well as sarcospan and a dramatic reduction in dystroglycan in adipocytes. We further demonstrate that β-sarcoglycan null mice, which lack the sarcoglycan complex in adipose tissue and skeletal muscle, are glucose-intolerant and exhibit whole body insulin resistance specifically due to impaired insulin-stimulated glucose uptake in skeletal muscles. Thus, our data demonstrate a novel function of the sarcoglycan complex in whole body glucose homeostasis and skeletal muscle metabolism, suggesting that the impairment of the skeletal muscle metabolism influences the pathogenesis of muscular dystrophy.

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Title: Subtitle: Sarcoglycan Complex: IMPLICATIONS FOR METABOLIC DEFECTS IN MUSCULAR DYSTROPHIES
Creators: Séverine Groh - From the
Haihong Zong - the
Matthew M Goddeeris - From the
Connie S Lebakken - From the
David Venzke - From the
Jeffrey E Pessin - the
Kevin P Campbell - From the
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.284(29), pp.19178-19182
DOI: 10.1074/jbc.C109.010728
PMID: 19494113
PMCID: PMC2740540
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: American Society for Biochemistry and Molecular Biology; 9650 Rockville Pike, Bethesda, MD 20814, U.S.A
Grant note: R01 AR051199-01 / National Institutes of Health
Language: English
Date published: 07/17/2009
Academic Unit: Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984020624302771

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