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Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance.

C Yang·K J Coker·J K Kim·S Mora·D C Thurmond·A C Davis·B Yang·R A Williamson·G I Shulman·J E Pessin
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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.

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AdipocytesAdipose Tissue, BrownAnimalsBiological TransportGlucoseGlucose Clamp TechniqueGlucose Tolerance TestGlucose Transporter Type 4GlycogenGlycolysisHeterozygoteInsulin ResistanceLiverMembrane ProteinsMiceMice, KnockoutMonosaccharide Transport ProteinsMuscle ProteinsMuscle, SkeletalQa-SNARE ProteinsJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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C Yang, K J Coker, J K Kim, S Mora, D C Thurmond, A C Davis, B Yang, R A Williamson, G I Shulman, J E Pessin. 2001. Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance.. https://doi.org/10.1172/jci12274

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