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

Shaikh Mizanoor Rahman, Agnieszka Dobrzyn, Pawel Dobrzyn, Seong Ho Lee, Makoto Miyazaki, James M. Ntambi

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

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.

Original languageEnglish
Pages (from-to)11110-11115
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number19
DOIs
StatePublished - Sep 16 2003

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