These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A dynamic system for suppression and re-expression of insulin and pervanadate bioresponses in rat adipocytes. Treatment with okadaic acid and staurosporine.
    Author: Shisheva A, Shechter Y.
    Journal: Biochem Pharmacol; 1994 Apr 29; 47(9):1537-44. PubMed ID: 8185665.
    Abstract:
    In previous studies, we demonstrated that while okadaic acid stimulates glucose metabolism, it suppresses the bioresponses of insulin itself in rat adipocytes (Shisheva and Shechter, Endocrinology 129: 2279-2288, 1991). Both stimulation and suppression were attributed to okadaic acid-dependent inhibition of protein phosphatases 1 and 2A. We report here that exposure of adipocytes to staurosporine prior to okadaic acid restored insulin-stimulated actions on glucose metabolism. The effect was half-maximal at staurosporine concentrations as low as 70 nM and was fully expressed (80-87% of the control) at 400-500 nM. Similarly, the insulin-like effect of pervanadate, which was also suppressed by okadaic acid, was restored completely with staurosporine pretreatment. Staurosporine was less effective in restoring cell responses inhibited by high concentrations of okadaic acid, or when added to the cells after okadaic acid. Cell resensitization was unique to staurosporine and could not be produced by various agents that reduce cellular protein kinase A- or protein kinase C-dependent phosphorylation, such as phenylisopropyl adenosine (PIA), K-252a and GF 109203X. Staurosporine (400 nM) partially reversed lipolysis induced by okadaic acid but not that induced by beta-adrenergic stimulation. PIA, which antagonized okadaic acid-induced lipolysis to the same extent as staurosporine, was not capable of restoring insulin responses. Further studies aimed at elucidating this reversing effect revealed that staurosporine did not reactivate okadaic acid-inhibited protein phosphatases 1 and 2A in both cellular and cell-free systems. In summary, we report here a unique dynamic system in which insulin and pervanadate bioeffects can be fully suppressed and again re-expressed without reactivation of protein phosphatase 1 or 2A. The precise site for both effects, although still obscure, appears to be downstream from autophosphorylated insulin receptor.
    [Abstract] [Full Text] [Related] [New Search]