Mechanisms of inhibition of lipolysis by insulin, vanadate and peroxovanadate in rat adipocytes
Författare
Summary, in English
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.
Avdelning/ar
Publiceringsår
1999
Språk
Engelska
Sidor
281-289
Publikation/Tidskrift/Serie
Biochemical Journal
Volym
339
Dokumenttyp
Artikel i tidskrift
Förlag
Portland Press
Ämne
- Biochemistry and Molecular Biology
Nyckelord
- diabetes
- insulin receptor substrate-1
- phosphodiesterase type 3B
- phosphoinositide 3-kinase
- cAMP-dependent protein kinase
Status
Published
Forskningsgrupp
- Insulin Signal Transduction
ISBN/ISSN/Övrigt
- ISSN: 0264-6021