PMID- 10903138
OWN - NLM
STAT- MEDLINE
DCOM- 20010118
LR  - 20211203
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 349 Pt 3
IP  - Pt 3
DP  - 2000 Aug 1
TI  - Contraction inhibits insulin-stimulated insulin receptor substrate-1/2-associated 
      phosphoinositide 3-kinase activity, but not protein kinase B activation or 
      glucose uptake, in rat muscle.
PG  - 775-81
AB  - The initial stages of insulin-stimulated glucose uptake are thought to involve 
      tyrosine phosphorylation of insulin receptor substrates (IRSs), which recruit and 
      activate phosphoinositide 3-kinase (PI 3-kinase), leading to the activation of 
      protein kinase B (PKB) and other downstream effectors. In contrast, contraction 
      stimulates glucose uptake via a PI 3-kinase-independent mechanism. The combined 
      effects of insulin and contraction on glucose uptake are additive. However, it 
      has been reported that contraction causes a decrease in insulin-stimulated 
      IRS-1-associated PI 3-kinase activity. To investigate this paradox, we have 
      examined the effects of contraction on insulin-stimulated glucose uptake and 
      proximal insulin-signalling events in isolated rat epitrochlearis muscle. 
      Stimulation by insulin or contraction produced a 3-fold increase in glucose 
      uptake, with the effects of simultaneous treatment by insulin and contraction 
      being additive. Wortmannin completely blocked the additive effect of insulin in 
      contracting skeletal muscle, indicating that this is a PI 3-kinase-dependent 
      effect. Insulin-stimulated recruitment of PI 3-kinase to IRS-1 was unaffected by 
      contraction; however, insulin produced no discernible increase in PI 3-kinase 
      activity in IRS-1 or IRS-2 immunocomplexes in contracting skeletal muscle. 
      Consistent with this, contraction inhibited insulin-stimulated p70(S6K) 
      activation. In contrast, insulin-stimulated activation of PKB was unaffected by 
      contraction. Thus, in contracting skeletal muscle, insulin stimulates glucose 
      uptake and activates PKB, but not p70(S6K), by a PI 3-kinase-dependent mechanism 
      that is independent of changes in IRS-1- and IRS-2-associated PI 3-kinase 
      activity.
FAU - Whitehead, J P
AU  - Whitehead JP
AD  - Department of Medicine, University of Cambridge, Addenbrooke's Hospital, 
      Cambridge CB2 2QR, U.K. J.Whitehead@cmcb.uq.edu.au
FAU - Soos, M A
AU  - Soos MA
FAU - Aslesen, R
AU  - Aslesen R
FAU - O'rahilly, S
AU  - O'rahilly S
FAU - Jensen, J
AU  - Jensen J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Androstadienes)
RN  - 0 (Insulin)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (Irs2 protein, rat)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Enzyme Activation
MH  - Glucose/*metabolism
MH  - Insulin/metabolism
MH  - Insulin Receptor Substrate Proteins
MH  - Intracellular Signaling Peptides and Proteins
MH  - Male
MH  - *Muscle Contraction
MH  - Muscle, Skeletal/*enzymology/metabolism/physiology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphoproteins/*metabolism
MH  - Phosphorylation
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Rats, Wistar
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Wortmannin
PMC - PMC1221204
EDAT- 2000/07/21 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/02/01
CRDT- 2000/07/21 11:00
PHST- 2000/07/21 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/07/21 11:00 [entrez]
PHST- 2001/02/01 00:00 [pmc-release]
AID - 10.1042/bj3490775 [doi]
PST - ppublish
SO  - Biochem J. 2000 Aug 1;349 Pt 3(Pt 3):775-81. doi: 10.1042/bj3490775.