TY - JOUR
T1 - Control of exercise-stimulated muscle glucose uptake by GLUT4 is dependent on glucose phosphorylation capacity in the conscious mouse
AU - Fueger, Patrick T.
AU - Hess, Holli S.
AU - Posey, Kelly A.
AU - Bracy, Deanna P.
AU - Pencek, R. Richard
AU - Charron, Maureen J.
AU - Wasserman, David H.
PY - 2004/12/3
Y1 - 2004/12/3
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M408312200
DO - 10.1074/jbc.M408312200
M3 - Article
C2 - 15456776
AN - SCOPUS:10944248846
SN - 0021-9258
VL - 279
SP - 50956
EP - 50961
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 49
ER -