PMID- 12865258
OWN - NLM
STAT- MEDLINE
DCOM- 20031120
LR  - 20131121
IS  - 0193-1849 (Print)
IS  - 0193-1849 (Linking)
VI  - 285
IP  - 5
DP  - 2003 Nov
TI  - Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in 
      oxidative muscles of mice.
PG  - E958-63
AB  - Muscle glucose uptake (MGU) is distributively controlled by three serial steps: 
      delivery of glucose to the muscle membrane, transport across the muscle membrane, 
      and intracellular phosphorylation to glucose 6-phosphate by hexokinase (HK). 
      During states of high glucose fluxes such as moderate exercise, the HK activity 
      is of increased importance, since augmented muscle perfusion increases glucose 
      delivery, and increased GLUT4 at the cell membrane increases glucose transport. 
      Because HK II overexpression augments exercise-stimulated MGU, it was 
      hypothesized that a reduction in HK II activity would impair exercise-stimulated 
      MGU and that the magnitude of this impairment would be greatest in tissues with 
      the largest glucose requirement. To this end, mice with a HK II partial knockout 
      (HK+/-) were compared with their wild-type control (WT) littermates during either 
      sedentary or moderate exercise periods. Rg, an index of glucose metabolism, was 
      measured using 2-deoxy-[3H]glucose. No differences in glucose metabolism were 
      detected between sedentary groups. The increase in Rg due to exercise was 
      impaired in the highly oxidative heart and soleus muscles of HK+/- compared with 
      WT mice (7 +/- 10 vs. 29 +/- 9 and 8 +/- 3 vs. 25 +/- 7 micromol. 100 g-1. min-1, 
      respectively). However, the increase in Rg due to exercise was not altered in 
      gastrocnemius and superficial vastus lateralis muscles in HK+/- and WT mice (8 
      +/- 2 vs. 12 +/- 3 and 5 +/- 2 vs. 8 +/- 2 micromol. 100 g-1. min-1, 
      respectively). In conclusion, MGU is impaired by reductions in HK activity during 
      exercise, a physiological condition characterized by high glucose flux. This 
      impairment is critically dependent on the tissue's glucose metabolic rate and 
      correlates with tissue oxidative capacity.
FAU - Fueger, Patrick T
AU  - Fueger PT
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, TN 37232-0615, USA. patrick.fueger@vanderbilt.edu
FAU - Heikkinen, Sami
AU  - Heikkinen S
FAU - Bracy, Deanna P
AU  - Bracy DP
FAU - Malabanan, Carlo M
AU  - Malabanan CM
FAU - Pencek, R Richard
AU  - Pencek RR
FAU - Laakso, Markku
AU  - Laakso M
FAU - Wasserman, David H
AU  - Wasserman DH
LA  - eng
GR  - R01 DK-54902/DK/NIDDK NIH HHS/United States
GR  - U24 DK-59637/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030715
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 (Fatty Acids, Nonesterified)
RN  - 0 (Insulin)
RN  - 10028-17-8 (Tritium)
RN  - 9005-79-2 (Glycogen)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Blood Glucose/analysis
MH  - Body Weight
MH  - Deoxyglucose/metabolism
MH  - Fasting
MH  - Fatty Acids, Nonesterified/blood
MH  - Glucose/*metabolism
MH  - Glycogen/analysis/metabolism
MH  - Hexokinase/*deficiency/physiology
MH  - Insulin/blood
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred DBA
MH  - Mice, Knockout
MH  - Muscle, Skeletal/*metabolism
MH  - Myocardium/chemistry
MH  - Oxidation-Reduction
MH  - *Physical Exertion
MH  - Tritium
EDAT- 2003/07/17 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/07/17 05:00
PHST- 2003/07/17 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/07/17 05:00 [entrez]
AID - 00190.2003 [pii]
AID - 10.1152/ajpendo.00190.2003 [doi]
PST - ppublish
SO  - Am J Physiol Endocrinol Metab. 2003 Nov;285(5):E958-63. doi: 
      10.1152/ajpendo.00190.2003. Epub 2003 Jul 15.