Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle

被引:154
作者
Rahman, SM
Dobrzyn, A
Dobrzyn, P
Lee, SH
Miyazaki, M
Ntambi, JM [1 ]
机构
[1] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA
关键词
D O I
10.1073/pnas.1934571100
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We have shown previously that mice with a targeted disruption in the stearoyl-CoA desaturase 1 gene (SCD1(-/-)) have increased insulin sensitivity compared with control mice. Here we show that the SCD1(-/-) mice have increased insulin signaling in muscle. The basal tyrosine phosphorylation of the insulin receptor and insulin receptor substrates 1 and 2 are elevated. The tyrosine phosphorylation of insulin-like growth factor-1 receptor was similar between SCD1(+/+) and SCD1(-/-) mice. The association of insulin receptor substrates 1 and 2 with alphap85 subunit of phosphatidyl-inositol 3-kinase as well as the phosphorylation of Akt-Ser-473 and Akt-Thr-308 are also elevated in the SCD1(-/-) mice. Interestingly, the mRNA levels, protein mass, and activity of the protein-tyrosine phosphatase-1B implicated in the attenuation of the insulin signal are reduced in the SCD1(-/-) mice, whereas the levels of the leukocyte antigen-related protein phosphatase are similar between two groups of mice. The content of glucose transporter 4 in the plasma membrane and basal as well as insulin-mediated glucose uptake are increased in the SCD1(-/-) mice. In addition, the muscle glycogen content and the activities of glycogen synthase and phosphorylase are increased in the SCD1(-/-) mice. We hypothesize that loss of SCD1 function induces increased insulin signaling at least in part by a reduction in the expression of protein-tyrosine phosphatase 1B. SCD1 could be a therapeutic target in the treatment of diabetes.
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页码:11110 / 11115
页数:6
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