Stearoyl-CoA desaturase 1 deficiency elevates insulin-signaling components and down-regulates protein-tyrosine phosphatase 1B in muscle.
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.
Rahman
Shaikh Mizanoor
SM
Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Dobrzyn
Agnieszka
A
Dobrzyn
Pawel
P
Lee
Seong-Ho
SH
Miyazaki
Makoto
M
Ntambi
James M
JM
D000818:Animals; D015536:Down-Regulation; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000096:biosynthesis; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D015398:Signal Transduction; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000502:physiology*
D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse; D006003:Glycogen; D013230:Stearoyl-CoA Desaturase; D017027:Protein Tyrosine Phosphatases