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Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in rat adipocytes

Castan, Isabelle; Wijkander, Jonny; Manganiello, V and Degerman, Eva LU (1999) In Biochemical Journal 339. p.281-289
Abstract
Vanadate and peroxovanadate (pV), potent inhibitors of tyrosine phosphatases, mimic several of the metabolic actions of insulin. Here we compare the mechanisms for the anti-lipolytic action of insulin, vanadate and pV in rat adipocytes. Vanadate (5 mM) and pV (0.01 mM) inhibited lipolysis induced by 0.01-1 microM isoprenaline, vanadate being more and pV less efficient than insulin (1 nM). A loss of anti-lipolytic effect of pV was observed by increasing the concentration of isoprenaline and/or pV. pV induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 to a greater extent than insulin, whereas vanadate affected these components little if at all. In addition, only a higher concentration (0.1 mM) of pV... (More)
Vanadate and peroxovanadate (pV), potent inhibitors of tyrosine phosphatases, mimic several of the metabolic actions of insulin. Here we compare the mechanisms for the anti-lipolytic action of insulin, vanadate and pV in rat adipocytes. Vanadate (5 mM) and pV (0.01 mM) inhibited lipolysis induced by 0.01-1 microM isoprenaline, vanadate being more and pV less efficient than insulin (1 nM). A loss of anti-lipolytic effect of pV was observed by increasing the concentration of isoprenaline and/or pV. pV induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 to a greater extent than insulin, whereas vanadate affected these components little if at all. In addition, only a higher concentration (0.1 mM) of pV induced the tyrosine phosphorylation of p85, the 85 kDa regulatory subunit of phosphoinositide 3-kinase (PI-3K). Vanadate activated PI-3K-independent (in the presence of 10 nM isoprenaline) and PI-3K-dependent (in the presence of 100 nM isoprenaline) anti-lipolytic pathways, both of which were found to be independent of phosphodiesterase type 3B (PDE3B). pV (0.01 mM), like insulin, activated PI-3K- and PDE3B-dependent pathways. However, the anti-lipolytic pathway of 0.1 mM pV did not seem to require insulin receptor substrate-1-associated PI-3K and was found to be partly independent of PDE3B. Vanadate and pV (only at 0.01 mM), like insulin, decreased the isoprenaline-induced activation of cAMP-dependent protein kinase. Overall, these results underline the complexity and the diversity in the mechanisms that regulate lipolysis. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
diabetes, insulin receptor substrate-1, phosphodiesterase type 3B, phosphoinositide 3-kinase, cAMP-dependent protein kinase
in
Biochemical Journal
volume
339
pages
281 - 289
publisher
Portland Press Limited
external identifiers
  • pmid:10191258
  • scopus:0033561373
ISSN
0264-6021
language
English
LU publication?
yes
id
3ee116d9-565c-4cf1-92a3-c40fdf6264d1 (old id 1115634)
alternative location
http://www.biochemj.org/bj/339/0281/3390281.pdf
date added to LUP
2008-07-08 10:40:54
date last changed
2017-09-17 07:53:01
@article{3ee116d9-565c-4cf1-92a3-c40fdf6264d1,
  abstract     = {Vanadate and peroxovanadate (pV), potent inhibitors of tyrosine phosphatases, mimic several of the metabolic actions of insulin. Here we compare the mechanisms for the anti-lipolytic action of insulin, vanadate and pV in rat adipocytes. Vanadate (5 mM) and pV (0.01 mM) inhibited lipolysis induced by 0.01-1 microM isoprenaline, vanadate being more and pV less efficient than insulin (1 nM). A loss of anti-lipolytic effect of pV was observed by increasing the concentration of isoprenaline and/or pV. pV induced tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 to a greater extent than insulin, whereas vanadate affected these components little if at all. In addition, only a higher concentration (0.1 mM) of pV induced the tyrosine phosphorylation of p85, the 85 kDa regulatory subunit of phosphoinositide 3-kinase (PI-3K). Vanadate activated PI-3K-independent (in the presence of 10 nM isoprenaline) and PI-3K-dependent (in the presence of 100 nM isoprenaline) anti-lipolytic pathways, both of which were found to be independent of phosphodiesterase type 3B (PDE3B). pV (0.01 mM), like insulin, activated PI-3K- and PDE3B-dependent pathways. However, the anti-lipolytic pathway of 0.1 mM pV did not seem to require insulin receptor substrate-1-associated PI-3K and was found to be partly independent of PDE3B. Vanadate and pV (only at 0.01 mM), like insulin, decreased the isoprenaline-induced activation of cAMP-dependent protein kinase. Overall, these results underline the complexity and the diversity in the mechanisms that regulate lipolysis.},
  author       = {Castan, Isabelle and Wijkander, Jonny and Manganiello, V and Degerman, Eva},
  issn         = {0264-6021},
  keyword      = {diabetes,insulin receptor substrate-1,phosphodiesterase type 3B,phosphoinositide 3-kinase,cAMP-dependent protein kinase},
  language     = {eng},
  pages        = {281--289},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in rat adipocytes},
  volume       = {339},
  year         = {1999},
}