Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance

Chunmei Yang, Kenneth J. Coker, Jason K. Kim, Silvia Mora, Debbie C. Thurmond, Ann C. Davis, Baoli Yang, Roger A. Williamson, Gerald I. Shulman, Jeffrey E. Pessin

Research output: Contribution to journalArticle

87 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1311-1318
Number of pages8
JournalJournal of Clinical Investigation
Volume107
Issue number10
DOIs
StatePublished - Jan 1 2001

ASJC Scopus subject areas

  • Medicine(all)

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    Yang, C., 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. (2001). Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance. Journal of Clinical Investigation, 107(10), 1311-1318. https://doi.org/10.1172/JCI12274