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This Article Full Text Full Text (PDF) All Versions of this Article: 288/2/E381    most recent 00314.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (18) Citing Articles via Google Scholar Google Scholar Articles by Rahman, S. M. Articles by Ntambi, J. M. Search for Related Content PubMed PubMed Citation Articles by Rahman, S. M. Articles by Ntambi, J. M.

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

Departments of ¹Biochemistry and ²Nutritional Sciences, University of Wisconsin, Madison, Wisconsin

Submitted 15 July 2004 ; accepted in final form 6 October 2004

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, triglycerides, wax esters, and cholesterol esters. Previously, we showed that SCD1 deficiency elevates insulin-signaling components and downregulates protein-tyrosine phosphatase-1B (PTP-1B) in muscle, a major insulin-sensitive tissue. Here we found that, in brown adipose tissue (BAT), another insulin-sensitive tissue, the basal tyrosine phosphorylations of insulin receptor (IR) and IR substrates (IRS-1 and IRS-2) were upregulated in SCD1^–/– mice compared with wild-type mice. The association of IRS-1 and IRS-2 with the -p85 subunit of phosphatidylinositol 3-kinase as well as Akt-Ser⁴⁷³ and Akt-Thr³⁰⁸ phosphorylation is also elevated in the SCD1^–/– mice. The mRNA expression, protein levels, and activity of PTP-1B implicated in the attenuation of the insulin signal are reduced in the SCD1^–/– mice. The content of GLUT4 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 the 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.

stearoyl-coenzyme A desaturase; brown adipose tissue; insulin signaling

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