PMID- 15339747
OWN - NLM
STAT- MEDLINE
DCOM- 20050302
LR  - 20191210
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 288
IP  - 1
DP  - 2005 Jan
TI  - Leucine reduces the duration of insulin-induced PI 3-kinase activity in rat 
      skeletal muscle.
PG  - E86-91
AB  - 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.
FAU - Baum, Jamie I
AU  - Baum JI
AD  - Division of Nutritional Sciences, Department of Food Science and Human Nutrition, 
      University of Illinois Urbana-Champaign, Urbana, Illinois, USA.
FAU - O'Connor, Jason C
AU  - O'Connor JC
FAU - Seyler, Jennifer E
AU  - Seyler JE
FAU - Anthony, Tracy G
AU  - Anthony TG
FAU - Freund, Gregory G
AU  - Freund GG
FAU - Layman, Donald K
AU  - Layman DK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040831
PL  - United States
TA  - Am J Physiol Endocrinol Metab
JT  - American journal of physiology. Endocrinology and metabolism
JID - 100901226
RN  - 0 (Blood Glucose)
RN  - 0 (Carrier Proteins)
RN  - 0 (Dietary Carbohydrates)
RN  - 0 (Eif4ebp1 protein, rat)
RN  - 0 (Insulin)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - GMW67QNF9C (Leucine)
SB  - IM
MH  - Animals
MH  - Blood Glucose/drug effects/metabolism
MH  - Carrier Proteins/metabolism
MH  - Dietary Carbohydrates/pharmacology
MH  - Insulin/*blood
MH  - Intracellular Signaling Peptides and Proteins
MH  - Leucine/blood/*pharmacology
MH  - Male
MH  - Muscle, Skeletal/*drug effects/*enzymology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoproteins/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2004/09/02 05:00
MHDA- 2005/03/03 09:00
CRDT- 2004/09/02 05:00
PHST- 2004/09/02 05:00 [pubmed]
PHST- 2005/03/03 09:00 [medline]
PHST- 2004/09/02 05:00 [entrez]
AID - 00272.2004 [pii]
AID - 10.1152/ajpendo.00272.2004 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2005 Jan;288(1):E86-91. doi: 
      10.1152/ajpendo.00272.2004. Epub 2004 Aug 31.