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

Yenshou Lin, Samar I. Itani, Theodore G. Kurowski, David J. Dean, Zhijun Lou, Gordon C. Yaney, Neil B. Ruderman*


研究成果: 雜誌貢獻期刊論文同行評審

22 引文 斯高帕斯(Scopus)


Numerous studies have shown a correlation between changes in protein kinase C (PKC) distribution and/or activity and insulin resistance in skeletal muscle. To investigate which PKC isoforms might be involved and how they affect insulin action and signaling, studies were carried out in rat soleus muscle incubated with phorbol esters. Muscles preincubated for 1 h with I μM phorbol 12,13-dibutyrate (PDBu) showed an impaired ability of insulin to stimulate glucose incorporation into glycogen and a translocation of PKC-α, -βI, -θ, and -ε, and probably -βII, from the cytosol to membranes. Preincubation with 1 μM PDBu decreased activation of the insulin receptor tyrosine kinase by insulin and to an even greater extent the phosphorylation 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 lipid and oxidation to CO2 was unaffected. The results indicate that preincubation of skeletal muscle with phorbol ester leads to a translocation of multiple conventional and novel PKC isoforms and to an impairment of several, but not all, events in the insulin-signaling cascade. They also demonstrate that these changes are associated with an inhibition of insulin-stimulated glycogen synthesis but that, at the concentration of PDBu used here, glucose transport, its incorporation into lipid, and its oxidation to CO2 are unaffected.

頁(從 - 到)E8-E15
期刊American Journal of Physiology - Endocrinology and Metabolism
發行號1 44-1
出版狀態已發佈 - 2001

ASJC Scopus subject areas

  • 內分泌學、糖尿病和代謝
  • 生理學
  • 生理學(醫學)


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