Regulation of both glycogen synthase and PHAS-I by insulin in rat skeletal muscle involves mitogen-activated protein kinase-independent and rapamycin-sensitive pathways

Iñaki Azpiazu, Alan R. Saltiel, Anna De Paoli-Roach, John C. Lawrence

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Abstract

Incubating rat diaphragm muscles with insulin increased the glycogen synthase activity ratio (minus glucose 6-phosphate/plus glucose 6-phosphate) by approximately 2-fold. Insulin increased the activities of mitogen-activated protein (MAP) kinase and the Mr = 90,000 isoform of ribosomal protein S6 kinase (Rsk) by approximately 1.5-2.0-fold. Epidermal growth factor (EGF) was more effective than insulin in increasing MAP kinase and Rsk activity, but in contrast to insulin, EGF did not affect glycogen synthase activity. The activation of both MAP kinase and Rsk by insulin was abolished by incubating muscles with the MAP kinase kinase (MEK) inhibitor, PD 098059; however, the MEK inhibitor did not significantly reduce the effect of insulin on activating glycogen synthase. Incubating muscles with concentrations of rapamycin that inhibited activation of p70S6K abolished the activation of glycogen synthase. Insulin also increased the phosphorylation of PHAS-I (phosphorylated heat- and acid-stable protein) and promoted the dissociation of the PHAS-I-eIF-4E complex. Increasing MAP kinase activity with EGF did not mimic the effect of insulin on PHAS-I phosphorylation, and the effect of insulin on increasing MAP kinase could be abolished with the MEK inhibitor without decreasing the effect of insulin on PHAS-I. The effects of insulin on PHAS-I were attenuated by rapamycin. Thus, activation of the MAP kinase/Rsk signaling pathway appears to be neither necessary nor sufficient for insulin action on glycogen synthase and PHAS-I in rat skeletal muscle. The results indicate that the effects of insulin on increasing the synthesis of glycogen and protein in skeletal muscle, two of the most important actions of the hormone, involve a rapamycin-sensitive mechanism that may include elements of the p70S6K signaling pathway.

Original languageEnglish
Pages (from-to)5033-5039
Number of pages7
JournalJournal of Biological Chemistry
Volume271
Issue number9
StatePublished - Mar 1 1996

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Glycogen Synthase
Sirolimus
Mitogen-Activated Protein Kinases
Muscle
Rats
Skeletal Muscle
Hot Temperature
Insulin
Acids
Ribosomal Protein S6 Kinases
Proteins
Mitogen-Activated Protein Kinase Kinases
Chemical activation
Epidermal Growth Factor
70-kDa Ribosomal Protein S6 Kinases
Glucose-6-Phosphate
Phosphorylation
Muscles
Diaphragms
Diaphragm

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of both glycogen synthase and PHAS-I by insulin in rat skeletal muscle involves mitogen-activated protein kinase-independent and rapamycin-sensitive pathways. / Azpiazu, Iñaki; Saltiel, Alan R.; De Paoli-Roach, Anna; Lawrence, John C.

In: Journal of Biological Chemistry, Vol. 271, No. 9, 01.03.1996, p. 5033-5039.

Research output: Contribution to journalArticle

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