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Am J Physiol Endocrinol Metab (October 19, 2004). doi:10.1152/ajpendo.00314.2004
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Submitted on July 15, 2004
Accepted on October 6, 2004

Stearoyl-CoA desaturase 1 deficiency increases insulin signaling and glycogen accumulation in brown adipose tissue

Shaikh Mizanoor Rahman1, Agnieszka Dobrzyn1, Seong-Ho Lee1, Pawel Dobrzyn1, Makoto Miyazaki1, and James M. Ntambi2*

1 Department of Biochemistry, University of Wisconsin, Madison, WI, USA
2 Department of Biochemistry, University of Wisconsin, Madison, WI, USA; Department of Nutritional Sciences, University of Wisconsin, Madison, WI, USA

* To whom correspondence should be addressed. E-mail: ntambi{at}biochem.wisc.edu.

Stearoyl-CoA desaturase (SCD) catalyzes the synthesis of oleate (C18:1) and palmitoleate (C16:1) which are the main monounsaturated fatty acids of membrane phospholipids (PL), triglycerides (TG), wax esters and cholesterol esters. Previously, we showed SCD1 deficiency elevates insulin signaling components and downregulates protein-tyrosine phosphatase 1B in muscle a major insulin sensitive tissue. Here we found that in the brown adipose tissue another insulin sensitive tissue, the basal tyrosine phosphorylation of the insulin receptor (IR), and insulin receptor substrates (IRS-1 and IRS-2) were upregulated in SCD1-/- mice compared to the wild-type mice. The association of IRS-1 and IRS-2 with {alpha}p85 subunit of phosphatidylinositol 3-kinase as well as the Akt-Ser 473 and Akt-Thr 308 phosphorylation are also elevated in the SCD1- /- mice. The mRNA expression, protein levels, and activity of the protein-tyrosine phosphatase-1B (PTP-1B) implicated in the attenuation of the insulin signal, are reduced in the SCD1-/- mice. The content of glucose transporter 4 in the plasma membrane increased 2.5 fold and this was accompanied by a 6-fold increase in glucose uptake in BAT of SCD1-/- mice. The increased glucose uptake was associated with higher glycogen synthase activity and glycogen accumulation. In presence of insulin, [U- 14C]glucose incorporation into glycogen was increased in BAT of SCD1-/- mice. Taken together, these studies illustrate increased insulin signaling and increased glycogen metabolism in BAT of SCD1-/- mice.




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