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

Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E86-91. doi: 10.1152/ajpendo.00272.2004. Epub 2004 Aug 31.


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 (approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Carrier Proteins / metabolism
  • Dietary Carbohydrates / pharmacology
  • Insulin / blood*
  • Intracellular Signaling Peptides and Proteins
  • Leucine / blood
  • Leucine / pharmacology*
  • Male
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology*
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoproteins / metabolism
  • Rats
  • Rats, Sprague-Dawley


  • Blood Glucose
  • Carrier Proteins
  • Dietary Carbohydrates
  • Eif4ebp1 protein, rat
  • Insulin
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Leucine