Effects of rapamycin and wortmannin on the insulin stimulation of protein synthesis in rat skeletal muscle and L6 myoblasts

Scot Kimball, Christine V. Jurasinski, Thomas C. Vary, John C. Lawrence, Leonard "Jim" Jefferson

Research output: Contribution to journalArticle

Abstract

Insulin stimulated protein synthesis by 30% and 100%, respectively, in L6 myoblasts and perfused preparations of rat gastrocnemius muscle (gastroc). In L6 cells, both rapamydn and wortmannin blocked completely the stimulation of protein synthesis by insulin and prevented the insulin-indueed phosphorylation of p70s6k. In contrast, in gastroc. neither rapamycin nor wortmannin had any effect on the stimulation of protein synthesis by insulin even though both compounds prevented the phosphorylation of p70Sflk caused by insulin. In addition, wortmannin, but not rapamycin. blocked the increased uptake of glucose by the perfused hindlimb in response to insulin. In L6 myoblasts and gastroc insulin caused a 2 and 3.5- fold increase in phosphorylation of the elF-4E binding protein, PHAS-I. respectively, as well as a concomitant decrease in the amount of eIF-4E present in the PHASI-eIF-4E complex. In gastroc. rapamycin and wortmannin each decreased the effects of insulin on PHAS-I phosphorylation 35%; an attenuation of the association of PHAS-1 and eIF-4E was also observed. In contrast, in L6 cells, rapamycin partially blocked and wortmannin completely blocked the insulin-induced changes in PHAS-I phosphorylation and association ot PHAS-I and eIF-4E. Overall, the results suggest that insulin stimulates protein synthesis in rat skeletal muscle through a signal transduction pathway distinct from that utilized in L6 myoblasts. Supported bv NIH grant OM.W277(TCV). DK15658 (l.SJl. and DK28312and AR411SOUCI.).

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - Jan 1 1996

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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