Journal article
Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance
The Journal of clinical investigation, Vol.107(10), pp.1311-1318
05/15/2001
DOI: 10.1172/JCI12274
PMCID: PMC209300
PMID: 11375421
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.
Details
- Title: Subtitle
- Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance
- Creators
- Chunmei Yang - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USAKenneth J Coker - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USAJason K Kim - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USASilvia Mora - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USADebbie C Thurmond - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USAAnn C Davis - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USABaoli Yang - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USARoger A Williamson - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USAGerald I Shulman - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USAJeffrey E Pessin - Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.107(10), pp.1311-1318
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI12274
- PMID
- 11375421
- PMCID
- PMC209300
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 05/15/2001
- Academic Unit
- BioVentures Center; Obstetrics and Gynecology
- Record Identifier
- 9984083993902771
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