Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle

Citation
Ys. Lin et al., Inhibition of insulin signaling and glycogen synthesis by phorbol dibutyrate in rat skeletal muscle, AM J P-ENDO, 281(1), 2001, pp. E8-E15
Citations number
35
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
ISSN journal
0193-1849 → ACNP
Volume
281
Issue
1
Year of publication
2001
Pages
E8 - E15
Database
ISI
SICI code
0193-1849(200107)281:1<E8:IOISAG>2.0.ZU;2-W
Abstract
Numerous studies have shown a correlation between changes in protein kinase C (PKC) distribution and/or activity and insulin resistance in skeletal mu scle. To investigate which PKC isoforms might be involved and how they affe ct insulin action and signaling, studies were carried out in rat soleus mus cle incubated with phorbol esters. Muscles preincubated for 1 h with 1 muM phorbol 12,13-dibutyrate (PDBu) showed an impaired ability of insulin to st imulate glucose incorporation into glycogen and a translocation of PKC-alph a,-betaI, -theta, and -epsilon, and probably -beta II, from the cytosol to membranes. Preincubation with 1 mM PDBu decreased activation of the insulin receptor tyrosine kinase by insulin and to an even greater extent the phos phorylation of Akt/protein kinase B and glycogen synthase kinase-3. However , it failed to diminish the activation of phosphatidylinositol 3'-kinase by insulin. Despite these changes in signaling, the stimulation by insulin of glucose transport (2-deoxyglucose uptake) and glucose incorporation into l ipid and oxidation to CO2 was unaffected. The results indicate that preincu bation of skeletal muscle with phorbol ester leads to a translocation of mu ltiple conventional and novel PKC isoforms and to an impairment of several, but not all, events in the insulin-signaling cascade. They also demonstrat e that these changes are associated with an inhibition of insulin-stimulate d glycogen synthesis but that, at the concentration of PDBu used here, gluc ose transport, its incorporation into lipid, and its oxidation to CO2 are u naffected.