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

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 alphap85 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.

• Authors: Shaikh Mizanoor Rahman, Agnieszka Dobrzyn, Pawel Dobrzyn, Seong-Ho Lee, Makoto Miyazaki, James M Ntambi
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 100 Issue 19 Pg. 11110-5 (Sep 16 2003) ISSN: 0027-8424 [Print] United States
• PMID: 12960377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Glucose Transporter Type 4
• Insulin
• Monosaccharide Transport Proteins
• Muscle Proteins
• Slc2a4 protein, mouse
• Glycogen
• Stearoyl-CoA Desaturase
• Protein Tyrosine Phosphatases

Topics

• Animals
• Down-Regulation
• Glucose Transporter Type 4
• Glycogen (biosynthesis)
• Insulin (metabolism)
• Mice
• Mice, Knockout
• Monosaccharide Transport Proteins (metabolism)
• Muscle Proteins
• Muscle, Skeletal (enzymology, metabolism)
• Phosphorylation
• Protein Tyrosine Phosphatases (metabolism)
• Signal Transduction
• Stearoyl-CoA Desaturase (genetics, physiology)