PMID- 17639019
OWN - NLM
STAT- MEDLINE
DCOM- 20071113
LR  - 20131121
IS  - 1939-327X (Electronic)
IS  - 0012-1797 (Linking)
VI  - 56
IP  - 10
DP  - 2007 Oct
TI  - Phosphorylation barriers to skeletal and cardiac muscle glucose uptakes in 
      high-fat fed mice: studies in mice with a 50% reduction of hexokinase II.
PG  - 2476-84
AB  - OBJECTIVE: Muscle glucose uptake (MGU) is regulated by glucose delivery to, 
      transport into, and phosphorylation within muscle. The aim of this study was to 
      determine the role of limitations in glucose phosphorylation in the control of 
      MGU during either physiological insulin stimulation (4 mU x kg(-1) x min(-1)) or 
      exercise with chow or high-fat feeding. RESEARCH DESIGN AND METHODS: C57BL/6J 
      mice with (HK(+/-)) and without (WT) a 50% hexokinase (HK) II deletion were fed 
      chow or high-fat diets and studied at 4 months of age during a 120-min insulin 
      clamp or 30 min of treadmill exercise (n = 8-10 mice/group). 2-deoxy[(3)H]glucose 
      was used to measure R(g), an index of MGU. RESULTS: Body weight and fasting 
      arterial glucose were increased by high-fat feeding and partial HK II knockout 
      (HK(+/-)). Both high-fat feeding and partial HK II knockout independently created 
      fasting hyperinsulinemia, a response that was increased synergistically with 
      combined high-fat feeding and HK II knockout. Whole-body insulin action was 
      suppressed by approximately 25% with either high-fat feeding or partial HK II 
      knockout alone but by >50% when the two were combined. Insulin-stimulated R(g) 
      was modestly impaired by high-fat feeding and partial HK II knockout 
      independently ( approximately 15-20%) but markedly reduced by the two together ( 
      approximately 40-50%). Exercise-stimulated R(g) was reduced by approximately 50% 
      with high-fat feeding and partial HK II knockout alone and was not attenuated 
      further by combining the two. CONCLUSIONS: In summary, impairments in whole-body 
      metabolism and MGU due to high-fat feeding and partial HK II knockout combined 
      during insulin stimulation are additive. In contrast, combining high-fat feeding 
      and partial HK II knockout during exercise causes no greater impairment in MGU 
      than the two manipulations independently. This suggests that MGU is impaired 
      during exercise by high-fat feeding due to, in large part, a limitation in 
      glucose phosphorylation. Together, these studies show that the high-fat-fed mouse 
      is characterized by defects at multiple steps of the MGU system that are 
      precipitated by different physiological conditions.
FAU - Fueger, Patrick T
AU  - Fueger PT
AD  - Department of Molecular Physiology and Biophysics, Vanderbilt University School 
      of Medicine, Nashville, Tennessee, USA. patrick.fueger@duke.edu
FAU - Lee-Young, Robert S
AU  - Lee-Young RS
FAU - Shearer, Jane
AU  - Shearer J
FAU - Bracy, Deanna P
AU  - Bracy DP
FAU - Heikkinen, Sami
AU  - Heikkinen S
FAU - Laakso, Markku
AU  - Laakso M
FAU - Rottman, Jeffrey N
AU  - Rottman JN
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, N.I.H., Extramural
DEP - 20070716
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adipose Tissue/enzymology
MH  - Animals
MH  - Biological Transport
MH  - Blood Glucose/drug effects/metabolism
MH  - Glucose/*metabolism
MH  - Glucose Clamp Technique
MH  - Hexokinase/deficiency/*metabolism
MH  - Hyperinsulinism
MH  - Insulin/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Muscle, Skeletal/enzymology/*metabolism
MH  - Myocardium/enzymology/*metabolism
MH  - Phosphorylation
MH  - Physical Endurance
MH  - Physical Exertion
MH  - Reference Values
EDAT- 2007/07/20 09:00
MHDA- 2007/11/14 09:00
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2007/11/14 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
AID - db07-0532 [pii]
AID - 10.2337/db07-0532 [doi]
PST - ppublish
SO  - Diabetes. 2007 Oct;56(10):2476-84. doi: 10.2337/db07-0532. Epub 2007 Jul 16.