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|Title:||Syntaxin 4 heteozygous knock-out mice develop muscle insulin resistance|
Coker, Kenneth J.
Kim, Jason K.
Mora Fayos, Sílvia
Thurmond, Debbie C.
Davis, Ann C.
Williamson, Roger A.
Shulman, Gerald I.
Pessin, Jeffrey E.
Resistència a la insulina
|Publisher:||American Society for Clinical Investigation|
|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.|
|Note:||Reproducció del document publicat a: https://doi.org/10.1172/jci12274|
|It is part of:||Journal of Clinical Investigation, 2001, vol. 107, p. 1311-1318.|
|Appears in Collections:||Articles publicats en revistes (Bioquímica i Biomedicina Molecular)|
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