PMID- 10455163
OWN - NLM
STAT- MEDLINE
DCOM- 19990930
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 35
DP  - 1999 Aug 27
TI  - Insulin and exercise decrease glycogen synthase kinase-3 activity by different
      mechanisms in rat skeletal muscle.
PG  - 24896-900
AB  - Glycogen synthase activity is increased in response to insulin and exercise in
      skeletal muscle. Part of the mechanism by which insulin stimulates glycogen
      synthesis may involve phosphorylation and activation of Akt, serine
      phosphorylation and deactivation of glycogen synthase kinase-3 (GSK-3), leading
      to dephosphorylation and activation of glycogen synthase. To study Akt and GSK-3 
      regulation in muscle, time course experiments on the effects of insulin injection
      and treadmill running exercise were performed in hindlimb skeletal muscle from
      male rats. Both insulin and exercise increased glycogen synthase activity
      (%I-form) by 2-3-fold over basal. Insulin stimulation significantly increased Akt
      phosphorylation and activity, whereas exercise had no effect. The time course of 
      the insulin-stimulated increase in Akt was closely matched by GSK-3alpha Ser(21) 
      phosphorylation and a 40-60% decrease in GSK-3alpha and GSK-3beta activity.
      Exercise also deactivated GSK-3alpha and beta activity by 40-60%. However, in
      contrast to the effects of insulin, there was no change in Ser(21)
      phosphorylation in response to exercise. Tyrosine dephosphorylation of GSK-3,
      another putative mechanism for GSK-3 deactivation, did not occur with insulin or 
      exercise. These data suggest the following: 1) GSK-3 is constitutively active and
      tyrosine phosphorylated under basal conditions in skeletal muscle, 2) both
      exercise and insulin are effective regulators of GSK-3 activity in vivo, 3) the
      insulin-induced deactivation of GSK-3 occurs in response to increased Akt
      activity and GSK-3 serine phosphorylation, and 4) there is an Akt-independent
      mechanism for deactivation of GSK-3 in skeletal muscle.
FAU - Markuns, J F
AU  - Markuns JF
AD  - Research Division, Joslin Diabetes Center, and the Department of Medicine,
      Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
      02215, USA.
FAU - Wojtaszewski, J F
AU  - Wojtaszewski JF
FAU - Goodyear, L J
AU  - Goodyear LJ
LA  - eng
GR  - AR42238/AR/NIAMS NIH HHS/United States
GR  - AR45670/AR/NIAMS NIH HHS/United States
GR  - T32-DR07260-21/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Insulin)
RN  - 17885-08-4 (Phosphoserine)
RN  - 21820-51-9 (Phosphotyrosine)
RN  - EC 2.4.1.11 (Glycogen Synthase)
RN  - EC 2.7.11.- (Glycogen Synthase Kinases)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
SB  - IM
SB  - S
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism
MH  - Glycogen Synthase/metabolism
MH  - Glycogen Synthase Kinase 3
MH  - Glycogen Synthase Kinases
MH  - Insulin/*pharmacology
MH  - Kinetics
MH  - Male
MH  - Muscle, Skeletal/*metabolism
MH  - Phosphorylation
MH  - Phosphoserine/metabolism
MH  - Phosphotyrosine/metabolism
MH  - Physical Conditioning, Animal
MH  - Protein-Serine-Threonine Kinases/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 1999/08/24 00:00
MHDA- 1999/08/24 00:01
CRDT- 1999/08/24 00:00
PHST- 1999/08/24 00:00 [pubmed]
PHST- 1999/08/24 00:01 [medline]
PHST- 1999/08/24 00:00 [entrez]
AID - 10.1074/jbc.274.35.24896 [doi]
AID - S0021-9258(19)55429-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 27;274(35):24896-900. doi: 10.1074/jbc.274.35.24896.