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Publication
Regulation of insulin-stimulated muscle glucose uptake in the conscious mouse:
role of glucose transport is dependent on glucose phosphorylation capacity.
Authors Fueger PT, Hess HS, Bracy DP, Pencek RR, Posey KA, Charron MJ, Wasserman DH
Submitted By David Wasserman on 11/6/2007
Status Published
Journal Endocrinology
Year 2004
Date Published
Volume : Pages 145 : 4912 - 4916
PubMed Reference 15284204
Abstract Previous work suggests that normal GLUT4 content is sufficient for increases in
muscle glucose uptake (MGU) during hyperinsulinemia, because glucose
phosphorylation is the more formidable barrier to insulin-stimulated MGU. It was
hypothesized that a partial ablation of GLUT4 would not impair
insulin-stimulated MGU when glucose phosphorylation capacity is normal but would
do so when glucose phosphorylation capacity is increased. Thus, chow-fed
C57BL/6J mice with a GLUT4 partial knockout (GLUT4(+/-)), hexokinase II
overexpression (HK(Tg)), or both (HK(Tg) + GLUT4(+/-)) and wild-type littermates
were studied. Carotid artery and jugular vein catheters were implanted for
sampling and infusions at 4 months of age. After a 5-d recovery, 5-h fasted mice
(n = 8-11/group) underwent a 120-min saline infusion or insulin clamp (4
mU/kg.min insulin with glucose maintained at 165 mg/dl) and received a
2-deoxy[(3)H]glucose bolus to provide an index of MGU (R(g)) for the soleus,
gastrocnemius, and superficial vastus lateralis. Basal R(g) from all muscles
studied from saline-infused mice were not changed by any of the genetic
modifications. HK(Tg) mice had augmented insulin-stimulated R(g) in all muscles
studied compared with remaining genotypes. Insulin-stimulated R(g) was not
impaired in any of the muscles studied from GLUT4(+/-) mice. However, the
enhanced insulin-stimulated R(g) created by HK overexpression was ablated in
HK(Tg) + GLUT4(+/-) mice. Thus, a 50% reduction of normal GLUT4 content in the
presence of normal HK activity does not impair insulin-stimulated MGU. However,
when the glucose phosphorylation barrier is lowered by HK overexpression, GLUT4
availability becomes a limitation to insulin-stimulated MGU.




Strains
StrainDevelopment StatusCreation MethodOptions
C57BL/6J-Slc2a4+/- Tg(Hk)Not Applicableknockout
View
C57BL/6J-Slc2a4tm1Mch/+ Tg(OE-Hk2)Not Applicableknockout
View
C57BL/6J-Slc2a4tm1Mch Tg(Hk2)Phenotyping ongoingtransgenic
View
C57BL/6J-Slc2a4tm1Mch Tg(OE-Hk2)Phenotyping ongoingknockout
View


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