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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1115634
- author
- Castan, Isabelle
; Wijkander, Jonny
; Manganiello, V
and Degerman, Eva
LU
- organization
- publishing date
- 1999
- 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
- 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
- 2016-04-01 16:57:50
- date last changed
- 2022-02-28 00:48:39
@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}},
keywords = {{diabetes; insulin receptor substrate-1; phosphodiesterase type 3B; phosphoinositide 3-kinase; cAMP-dependent protein kinase}},
language = {{eng}},
pages = {{281--289}},
publisher = {{Portland Press}},
series = {{Biochemical Journal}},
title = {{Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in rat adipocytes}},
url = {{http://www.biochemj.org/bj/339/0281/3390281.pdf}},
volume = {{339}},
year = {{1999}},
}