Control of exercise-stimulated muscle glucose uptake by GLUT4 is dependent on glucose phosphorylation capacity in the conscious mouse

Patrick T. Fueger, Holli S. Hess, Kelly A. Posey, Deanna P. Bracy, R. Richard Pencek, Maureen J. Charron, David H. Wasserman

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48 Scopus citations


Previous work suggests that normal GLUT4 content is sufficient for increases in muscle glucose uptake (MGU) during exercise because GLUT4 overexpression does not increase exercise-stimulated MGU. Instead of glucose transport, glucose phosphorylation is a primary limitation of exercise-stimulated MGU. It was hypothesized that a partial ablation of GLUT4 would not impair exercise-stimulated MGU when glucose phosphorylation capacity is normal but would do so when glucose phosphorylation capacity was increased. Thus, C57BL/6J mice with hexokinase II (HKII) overexpression (HKTg), a GLUT4 partial knock-out (G4+/-), or both (HKTg + G4 +/-) and wild-type (WT) littermates were implanted with carotid artery and jugular vein catheters for sampling and infusions at 4 months of age. After a 7-day recovery, 5-h fasted mice remained sedentary or ran on a treadmill at 0.6 mph for 30 min (n = 9-12 per group) and received a bolus of 2-deoxy[3H]glucose to provide an index of MGU (Rg). Arterial blood glucose and plasma insulin concentrations were similar in WT, G4+/-, HKTg, and HKTg + G4+/- mice. Sedentary Rg values were the same in all genotypes in all muscles studied, confirming that glucose transport is a significant barrier to basal glucose uptake. Gastrocnemius and soleus Rg were greater in exercising compared with sedentary mice in all genotypes. During exercise, G4+/- mice had a marked increase in blood glucose that was corrected by the addition of HK II overexpression. Exercise Rg (μmol/100g/min) was not different between WT and G4+/- mice in the gastrocnemius (24 ± 5 versus 21 ± 2) or the soleus (54 ± 6 versus 70 ± 7). In contrast, the enhanced exercise Rg observed in HKTg mice compared with that in WT mice was absent in HKTg + G4+/- mice in both the gastrocnemius (39 ± 7 versus 22 ± 6) and the soleus (98 ± 13 versus 65 ± 13). Thus, glucose transport is not a significant barrier to exercise-stimulated MGU despite a 50% reduction in GLUT4 content when glucose phosphorylation capacity is normal. However, when glucose phosphorylation capacity is increased by HK II overexpression, GLUT4 availability becomes a marked limitation to exercise-stimulated MGU.

Original languageEnglish (US)
Pages (from-to)50956-50961
Number of pages6
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Dec 3 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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