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PMID: 11375421 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance.

The Journal of clinical investigation ·Vol. 107 ·No. 10 ·2001-05-00 ·Pages 1311-8

Yang C, Coker KJ, Kim JK, Mora S, Thurmond DC, Davis AC, Yang B, Williamson RA, Shulman GI, Pessin JE

Abstract

To investigate the physiological function of syntaxin 4 in the regulation of GLUT4 vesicle trafficking, we used homologous recombination to generate syntaxin 4-knockout mice. Homozygotic disruption of the syntaxin 4 gene results in early embryonic lethality, whereas heterozygous knockout mice, Syn4(+/-), had normal viability with no significant impairment in growth, development, or reproduction. However, the Syn4(+/-) mice manifested impaired glucose tolerance with a 50% reduction in whole-body glucose uptake. This defect was attributed to a 50% reduction in skeletal muscle glucose transport determined by 2-deoxyglucose uptake during hyperinsulinemic-euglycemic clamp procedures. In parallel, insulin-stimulated GLUT4 translocation in skeletal muscle was also significantly reduced in these mice. In contrast, Syn4(+/-) mice displayed normal insulin-stimulated glucose uptake and metabolism in adipose tissue and liver. Together, these data demonstrate that syntaxin 4 plays a critical physiological role in insulin-stimulated glucose uptake in skeletal muscle. Furthermore, reduction in syntaxin 4 protein levels in this tissue can account for the impairment in whole-body insulin-stimulated glucose metabolism in this animal model.

MeSH Terms
Adipocytes/physiology Adipose Tissue, Brown Animals Biological Transport Glucose/metabolism Glucose Clamp Technique Glucose Tolerance Test Glucose Transporter Type 4 Glycogen/metabolism Glycolysis Heterozygote Insulin Resistance/genetics Liver/metabolism Membrane Proteins/genetics Mice Mice, Knockout Monosaccharide Transport Proteins/metabolism Muscle Proteins Muscle, Skeletal/physiology Qa-SNARE Proteins
Chemicals
Glucose Transporter Type 4 Membrane Proteins Monosaccharide Transport Proteins Muscle Proteins Qa-SNARE Proteins Slc2a4 protein, mouse Glycogen Glucose
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Yang C
Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA.
Coker K J
Kim J K
Mora S
Thurmond D C
Davis A C
Yang B
Williamson R A
Shulman G I
Pessin J E
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI12274
Published
2001-05-00
Pages
1311-8
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC209300
Subset
IM
Grants
NIDDK NIH HHS · DK-55811 · United States
NIDDK NIH HHS · F32 DK009813 · United States
NIDDK NIH HHS · R01 DK040936 · United States
NIDDK NIH HHS · R01 DK055811 · United States
NIDDK NIH HHS · R01 DK080756 · United States
NIDDK NIH HHS · DK-25295 · United States
Corrections
CommentIn
PMID: 11375407
External Links
PubMed source DOI: 10.1172/JCI12274 PMC Full Text View journal details
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