We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
C[sub 2]-Ceramide Influences the Expression and Insulin-Mediated Regulation of Cyclic Nucleotide Phosphodiesterase 3B and Lipolysis in 3T3-L1 Adipocytes.
- Authors
Jie Mei; Holst, Lena Stenson; Landström, Tova Rahn; Holm, Cecilia; Brindley, David; Manganiello, Vincent; Degerman, Eva
- Abstract
Cyclic nucleotide phosphodiesterase (PDE) 3B plays an important role in the antilipolytic action of insulin and, thereby, the release of fatty acids from adipocytes. Increased concentrations of circulating fatty acids as a result of elevated or unrestrained lipolysis cause insulin resistance. The lipolytic action of tumor necrosis factor (TNF)-α is thought to be one of the mechanisms by which TNF-α induces insulin resistance. Ceramide is the suggested second messenger of TNF-α action, and in this study, we used 3T3-L1 adipocytes to investigate the effects of C[sub 2]-ceramide (a short-chain ceramide analog) on the expression and regulation of PDE3B and lipolysis. Incubation of adipocytes with 100 μmol/l C[sub 2]-ceramide (N-acetyl-sphingosine) resulted in a time-dependent decrease of PDE3B activity, accompanied by decreased PDE3B protein expression. C[sub 2]-ceramide, in a time- and dose-dependent manner, stimulated lipolysis, an effect that was blocked by H-89, an inhibitor of protein kinase A. These ceramide effects were prevented by 20 μmol/l troglitazone, an antidiabetic drug. In addition to downregulation of PDE3B, the antilipolytic action of insulin was decreased by ceramide treatment. These results, together with data from other studies on PDE3B and lipolysis in diabetic humans and animals, suggest a novel pathway by which ceramide induces insulin resistance. Furthermore, PDE3B is demonstrated to be a target for troglitazone action in adipocytes.
- Subjects
AMIDES; CYCLIC nucleotide phosphodiesterases; LIPOLYSIS; INSULIN resistance
- Publication
Diabetes, 2002, Vol 51, Issue 3, p631
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/diabetes.51.3.631