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C(2)-ceramide influences the expression and insulin-mediated regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 adipocytes.

Mei, Jie LU ; Stenson, Lena LU ; Landström, Tova LU ; Holm, Cecilia LU ; Brindley, David; Manganiello, Vincent and Degerman, Eva LU (2002) In Diabetes 51(3). p.631-637
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)-alpha is thought to be one of the mechanisms by which TNF-alpha induces insulin resistance. Ceramide is the suggested second messenger of TNF-alpha action, and in this study, we used 3T3-L1 adipocytes to investigate the effects of C(2)-ceramide (a short-chain ceramide analog) on the expression and regulation of PDE3B and lipolysis. Incubation of adipocytes with 100 micromol/l C(2)-ceramide... (More)
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)-alpha is thought to be one of the mechanisms by which TNF-alpha induces insulin resistance. Ceramide is the suggested second messenger of TNF-alpha action, and in this study, we used 3T3-L1 adipocytes to investigate the effects of C(2)-ceramide (a short-chain ceramide analog) on the expression and regulation of PDE3B and lipolysis. Incubation of adipocytes with 100 micromol/l C(2)-ceramide (N-acetyl-sphingosine) resulted in a time-dependent decrease of PDE3B activity, accompanied by decreased PDE3B protein expression. C(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 micromol/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. (Less)
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keywords
Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors, Drug Interactions, Enzyme Inhibitors/pharmacology, Insulin/*pharmacology, Insulin Resistance, Isoquinolines/pharmacology, Tumor Necrosis Factor/pharmacology, Transcription Factors/genetics, Thiazoles/pharmacology, Non-U.S. Gov't, Support, Sphingosine/*analogs & derivatives/*pharmacology, Cytoplasmic and Nuclear/genetics, Receptors, Lipolysis/*drug effects, Mice, Chromans/pharmacology, Western, Blotting, Animal, 3', 5'-Cyclic-Nucleotide Phosphodiesterase/analysis/*metabolism, 3T3 Cells, Adipocytes/*metabolism
in
Diabetes
volume
51
issue
3
pages
631 - 637
publisher
American Diabetes Association Inc.
external identifiers
  • pmid:11872660
  • wos:000174167400011
ISSN
1939-327X
DOI
10.2337/diabetes.51.3.631
language
English
LU publication?
yes
id
227b5144-bfb7-4c7b-9d00-252ac850ea36 (old id 106591)
alternative location
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11872660&dopt=Abstract
date added to LUP
2007-07-18 09:55:59
date last changed
2016-04-16 03:37:05
@article{227b5144-bfb7-4c7b-9d00-252ac850ea36,
  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)-alpha is thought to be one of the mechanisms by which TNF-alpha induces insulin resistance. Ceramide is the suggested second messenger of TNF-alpha action, and in this study, we used 3T3-L1 adipocytes to investigate the effects of C(2)-ceramide (a short-chain ceramide analog) on the expression and regulation of PDE3B and lipolysis. Incubation of adipocytes with 100 micromol/l C(2)-ceramide (N-acetyl-sphingosine) resulted in a time-dependent decrease of PDE3B activity, accompanied by decreased PDE3B protein expression. C(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 micromol/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.},
  author       = {Mei, Jie and Stenson, Lena and Landström, Tova and Holm, Cecilia and Brindley, David and Manganiello, Vincent and Degerman, Eva},
  issn         = {1939-327X},
  keyword      = {Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors,Drug Interactions,Enzyme Inhibitors/pharmacology,Insulin/*pharmacology,Insulin Resistance,Isoquinolines/pharmacology,Tumor Necrosis Factor/pharmacology,Transcription Factors/genetics,Thiazoles/pharmacology,Non-U.S. Gov't,Support,Sphingosine/*analogs & derivatives/*pharmacology,Cytoplasmic and Nuclear/genetics,Receptors,Lipolysis/*drug effects,Mice,Chromans/pharmacology,Western,Blotting,Animal,3',5'-Cyclic-Nucleotide Phosphodiesterase/analysis/*metabolism,3T3 Cells,Adipocytes/*metabolism},
  language     = {eng},
  number       = {3},
  pages        = {631--637},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {C(2)-ceramide influences the expression and insulin-mediated regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 adipocytes.},
  url          = {http://dx.doi.org/10.2337/diabetes.51.3.631},
  volume       = {51},
  year         = {2002},
}