We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Critical role of stearoyl-CoA desaturase-1 (SCD1) in the onset of diet-induced hepatic insulin resistance.
- Authors
Gutiérrez-Juárez, Roger; Pocai, Alessandro; Mulas, Claudia; Ono, Hiraku; Bhanot, Sanjay; Monia, Brett P; Rossetti, Luciano
- Abstract
Stearoyl-CoA desaturase-1 (SCD1) catalyzes the synthesis of monounsaturated fatty acids from saturated fatty acids. Mice with a targeted disruption of Scd1 gene locus are lean and display increased insulin sensitivity. To examine whether Scd1 activity is required for the development of diet-induced hepatic insulin resistance, we used a sequence-specific antisense oligodeoxynucleotide (ASO) to lower hepatic Scd1 expression in rats and mice with diet-induced insulin resistance. Treatment of rats with Scd1 ASO markedly decreased liver Scd1 expression (approximately 80%) and total Scd activity (approximately 50%) compared with that in rats treated with scrambled ASO (control). Insulin clamp studies revealed severe hepatic insulin resistance in high-fat-fed rats and mice that was completely reversed by 5 days of treatment with Scd1 ASO. The latter treatment decreased glucose production (by approximately 75%), gluconeogenesis, and glycogenolysis. Downregulation of Scd1 also led to increased Akt phosphorylation and marked decreases in the expression of glucose-6-phosphatase (Glc-6-Pase) and phosphoenolpyruvate carboxykinase (PEPCK). Thus, Scd1 is required for the onset of diet-induced hepatic insulin resistance.
- Publication
The Journal of clinical investigation, 2006, Vol 116, Issue 6, p1686
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI26991