Leucine reduces the duration of insulin-induced PI 3-kinase activity in rat skeletal muscle

Jamie I. Baum, Jason C. O'Connor, Jennifer E. Seyler, Tracy G. Anthony, Gregory G. Freund, Donald K. Layman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Leucine (Leu) is known to stimulate translation initiation of protein synthesis at mammalian target of rapamycin (mTOR) in the insulin signaling pathway. However, potential feedback from mTOR to upstream aspects of the insulin signaling pathway remains controversial. This study evaluates the impact of a physiological oral dose of Leu and/or carbohydrate (CHO) on upstream elements of the insulin signaling pathway using phosphatidylinositol 3-kinase (PI 3-kinase) activity and glucose uptake as markers for insulin sensitivity and glucose homeostasis. Rats (∼200 g) were fasted 12 h and administered oral doses of CHO (1.31 g glucose, 1.31 g sucrose), Leu (270 mg), or CHO plus Leu. Animals were killed at 15, 30, 60, and 90 min after treatment. Plasma and gastrocnemius muscles were collected for analyses. Treatments were designed to produce elevated blood glucose and insulin with basal levels of Leu (CHO); elevated Leu with basal levels of glucose and insulin (Leu); or a combined increase of glucose, insulin, and Leu (CHO + Leu). The CHO treatment stimulated PI 3-kinase activity and glucose uptake with no effect on the downstream translation initiation factor eIF4E. Leu alone stimulated the release of the translation initiation factor eIF4E from 4E-BP1 with no effects on PI 3-kinase activity or glucose uptake. The CHO + Leu treatment reduced the magnitude and duration of the PI 3-kinase response but maintained glucose uptake similar to the CHO treatment and eIF4E levels similar to the Leu treatment. These findings demonstrate that Leu reduces insulin-stimulated PI 3-kinase activity while increasing downstream translation initiation and with no effect on net glucose transport in skeletal muscle.

Original languageEnglish (US)
Pages (from-to)E86-E91
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume288
Issue number1 51-1
DOIs
StatePublished - Jan 2005

Keywords

  • Glucose
  • Initiation factors
  • Insulin receptor substrate-1
  • Phosphatidylinositol 3-kinase

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Fingerprint Dive into the research topics of 'Leucine reduces the duration of insulin-induced PI 3-kinase activity in rat skeletal muscle'. Together they form a unique fingerprint.

Cite this