| First Author | Yang C | Year | 2001 |
| Journal | J Clin Invest | Volume | 107 |
| Issue | 10 | Pages | 1311-8 |
| PubMed ID | 11375421 | Mgi Jnum | J:69598 |
| Mgi Id | MGI:1934974 | Doi | 10.1172/JCI12274 |
| Citation | Yang C, et al. (2001) Syntaxin 4 heterozygous knockout mice develop muscle insulin resistance. J Clin Invest 107(10):1311-8 |
| abstractText | 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. |
