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

Content Provider	PubMed Central
Author	Rahman, Shaikh Mizanoor Dobrzyn, Agnieszka Pawel, Dobrzyn Lee, Seong-ho Miyazaki, Makoto Ntambi, James M.
Copyright Year	2003
Abstract	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 αp85 subunit of phosphatidylinositol 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.
Related Links	http://dx.doi.org/10.1073/pnas.1934571100
Ending Page	11115
Page Count	6
Starting Page	11110
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	19
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-09-16
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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