PMID- 12410639
OWN - NLM
STAT- MEDLINE
DCOM- 20030314
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 370
IP  - Pt 1
DP  - 2003 Feb 15
TI  - Control of glucose phosphorylation in L6 myotubes by compartmentalization, 
      hexokinase, and glucose transport.
PG  - 47-56
AB  - In muscle, insulin enhances influx of glucose and its conversion to glucose 
      6-phosphate (G6P) by hexokinase (HK). While effects of insulin on glucose 
      transport have been demonstrated, its effect on the activity of HK of cells has 
      not. In L6 myotubes treated for 24 h with insulin there was increased expression 
      of the HK isoform, HKII, and increased glucose phosphorylation without a 
      concomitant increase in glucose transport, indirectly suggesting that 
      phosphorylation of glucose was a target of insulin action [Osawa, Printz, 
      Whitesell and Granner (1995) Diabetes 44, 1426-1432]. In the present work the 
      same treatment led to a 2-fold rise in G6P, suggesting that transport and/or HK 
      were important targets of insulin action. We used a method to identify the site 
      of rate control involving the specificity of phosphorylation towards 
      2-deoxy-[1-14C]glucose and D-[2-3H]glucose. Glucose transport does not greatly 
      discriminate between these two tracers while HK shows increased specificity for 
      glucose. Specificity of the glucose phosphorylation of the cells increased with 
      addition of insulin and when extracellular glucose was raised. Specificity was 
      reduced at low glucose concentrations or when the inhibitor of transport, 
      cytochalasin B, was added. We conclude that transport and HK share nearly equal 
      control over glucose phosphorylation in these cells. A computer program was used 
      to test models for compatibility with the different types of experiments. The 
      predicted intracellular glucose and transport rates associated with 
      phosphorylation activity were lower than their measured values for the whole 
      cell. In the most likely model, 15+/-4% of the glucose transporters serve a 
      proportionate volume of the cytoplasm. Insulin activation of glucose 
      phosphorylation might then result from stimulation of these transporters together 
      with HK recruitment or relief from inhibition by G6P.
FAU - Whitesell, Richard R
AU  - Whitesell RR
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN 37232-6303, USA. richard.whitesell@vanderbilt.edu
FAU - Ardehali, Hossein
AU  - Ardehali H
FAU - Printz, Richard L
AU  - Printz RL
FAU - Beechem, Joseph M
AU  - Beechem JM
FAU - Knobel, Susan M
AU  - Knobel SM
FAU - Piston, David W
AU  - Piston DW
FAU - Granner, Daryl K
AU  - Granner DK
FAU - Van Der Meer, Wieb
AU  - Van Der Meer W
FAU - Perriott, Laureta M
AU  - Perriott LM
FAU - May, James M
AU  - May JM
LA  - eng
GR  - CA68485/CA/NCI NIH HHS/United States
GR  - DK20593/DK/NIDDK NIH HHS/United States
GR  - DK46867-06/DK/NIDDK NIH HHS/United States
GR  - DK53434/DK/NIDDK NIH 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  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Insulin)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Biological Transport
MH  - Cell Compartmentation
MH  - Cell Line
MH  - Glucose/*metabolism
MH  - Hexokinase/*metabolism
MH  - Insulin/pharmacology
MH  - Muscle, Skeletal/cytology/drug effects/enzymology/*metabolism
MH  - Phosphorylation
PMC - PMC1223141
EDAT- 2002/11/02 04:00
MHDA- 2003/03/15 04:00
PMCR- 2003/08/15
CRDT- 2002/11/02 04:00
PHST- 2002/10/31 00:00 [accepted]
PHST- 2002/10/24 00:00 [revised]
PHST- 2002/08/09 00:00 [received]
PHST- 2002/11/02 04:00 [pubmed]
PHST- 2003/03/15 04:00 [medline]
PHST- 2002/11/02 04:00 [entrez]
PHST- 2003/08/15 00:00 [pmc-release]
AID - BJ20021256 [pii]
AID - 10.1042/BJ20021256 [doi]
PST - ppublish
SO  - Biochem J. 2003 Feb 15;370(Pt 1):47-56. doi: 10.1042/BJ20021256.