PMID- 16550357
OWN - NLM
STAT- MEDLINE
DCOM- 20061024
LR  - 20181201
IS  - 0012-186X (Print)
IS  - 0012-186X (Linking)
VI  - 49
IP  - 5
DP  - 2006 May
TI  - Amino acids require glucose to enhance, through phosphoinositide-dependent 
      protein kinase 1, the insulin-activated protein kinase B cascade in 
      insulin-resistant rat adipocytes.
PG  - 1017-26
AB  - AIMS/HYPOTHESIS: Amino acids are well known to activate the mammalian target of 
      the rapamycin (mTOR) pathway in synergy with insulin to regulate cell functions. 
      Despite recent important advances, the mTOR signalling pathway is poorly 
      understood. Our previous results revealed a new pathway in which amino acids 
      permit insulin-induced activation of the protein kinase B (PKB)/mTOR pathway in 
      freshly isolated adipocytes when phosphatidylinositol 3-kinase (PI3K) is 
      inhibited. The aim of this study was to further investigate this pathway at the 
      molecular level. METHODS: We studied the effect of amino acids on PKB 
      phosphorylation in different cellular models or in freshly isolated adipocytes 
      incubated in different buffers, after a time course of insulin and amino acids 
      and in the presence of pharmacological inhibitors. To investigate the potential 
      role of amino acids in insulin action, the effect on glucose transport in obese 
      rat adipocytes following a high-fat diet was assessed. RESULTS: Insulin-induced 
      PKB phosphorylation is restored by amino acids in the presence of wortmannin in 
      adipose tissue explants and freshly isolated adipocytes, but not in cultured 
      adipocytes or hepatocytes. Moreover, amino acids require the presence of glucose 
      to phosphorylate PKB and to partially rescue glucose transport in a 
      PI3K-independent manner. The results also suggest that the amino acids act 
      through the phosphoinositide-dependent protein kinase 1. In addition, amino acids 
      were seen to improve insulin-stimulated glucose transport in adipocytes from 
      high-fat-fed rats. CONCLUSIONS/INTERPRETATION: This study suggests that amino 
      acids could enhance adipocyte insulin signalling in pathophysiological situations 
      such as insulin resistance associated with obesity.
FAU - Hinault, C
AU  - Hinault C
AD  - INSERM Unit 145, IFR 50, Faculty of Medicine, Avenue de Valombrose, F-06107, 
      Nice, Cedex 2, France.
FAU - Mothe-Satney, I
AU  - Mothe-Satney I
FAU - Gautier, N
AU  - Gautier N
FAU - Van Obberghen, E
AU  - Van Obberghen E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060321
PL  - Germany
TA  - Diabetologia
JT  - Diabetologia
JID - 0006777
RN  - 0 (Amino Acids)
RN  - 0 (Androstadienes)
RN  - 0 (Phosphatidylinositols)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Adipocytes/drug effects/enzymology/physiology
MH  - Amino Acids/*metabolism
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Biological Transport
MH  - Deoxyglucose/pharmacokinetics
MH  - Glucose/*metabolism/*pharmacology
MH  - *Insulin Resistance
MH  - Male
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphatidylinositols/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Wortmannin
EDAT- 2006/03/22 09:00
MHDA- 2006/10/25 09:00
CRDT- 2006/03/22 09:00
PHST- 2005/11/15 00:00 [received]
PHST- 2006/01/30 00:00 [accepted]
PHST- 2006/03/22 09:00 [pubmed]
PHST- 2006/10/25 09:00 [medline]
PHST- 2006/03/22 09:00 [entrez]
AID - 10.1007/s00125-006-0201-z [doi]
PST - ppublish
SO  - Diabetologia. 2006 May;49(5):1017-26. doi: 10.1007/s00125-006-0201-z. Epub 2006 
      Mar 21.