Vascular recruitment in forearm muscles during exercise

Palm, T.; Nielsen, Søren; Lassen, Niels A.

doi:10.1111/j.1475-097x.1983.tb00852.x

Cited by 12 publications

(6 citation statements)

References 7 publications

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“…During exercise, the massive hyperemia increases glucose delivery (32,33), and GLUT4 translocation to the sarcolemma (34 -36) increases glucose permeability. The net result of these two physiological events is that MGU markedly increases and the primary barrier to glucose influx in the working muscle shifts to glucose phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Control of Exercise-stimulated Muscle Glucose Uptake by GLUT4 Is Dependent on Glucose Phosphorylation Capacity in the Conscious Mouse

Fueger

Hess

Posey

et al. 2004

Journal of Biological Chemistry

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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 (HK Tg ), a GLUT4 partial knock-out (G4 ؉/؊ ), or both (HK Tg ؉ 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[ 3 H]glucose to provide an index of MGU (R g ). Arterial blood glucose and plasma insulin concentrations were similar in WT, G4 ؉/؊ , HK Tg , and HK Tg ؉ G4 ؉/؊ mice. Sedentary R g 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 R g 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 R g (mol/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 R g observed in HK Tg mice compared with that in WT mice was absent in HK Tg ؉ 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.Muscle glucose uptake (MGU) 1 can be separated into three sequential steps, i.e. delivery of glucose from the blood to the muscle, transport across the sarcolemma by a GLUT, and irreversible phosphorylation to glucose-6-phosphate by an HK isozyme. Each of these steps can serve as a barrier to MGU and, thus, are important in regulating glucose influx. During resting conditions, the transport step exerts the most control in regulating MGU, as GLUT1 (1-4) or GLUT4 (5, 6) overexpression augments basal MGU. Previous work suggests that normal GLUT4 content is sufficient for increases in MGU during exercise, because GLUT4 overexpression alone does not further increase exercise-stimulated MGU (7). Instead of glucose transport, glucose phosphorylation is a primary limitation of exercise-stimulated MGU (7-9). Heterozygous GLUT4 knock-out mice serve as a useful ...

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Section: Discussionmentioning

confidence: 99%

Control of Exercise-stimulated Muscle Glucose Uptake by GLUT4 Is Dependent on Glucose Phosphorylation Capacity in the Conscious Mouse

Fueger

Hess

Posey

et al. 2004

Journal of Biological Chemistry

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“…As the glycogen pool diminishes, the G-6-P levels will fall, thereby lowering the G-6-P inhibition of HK II and permitting more glucose entry. Another reason why the control shifts to glucose phosphorylation is that exercise also lowers the glucose delivery barrier by increasing blood flow and capillary recruitment and thus muscle perfusion (17,36). As the barriers to both glucose delivery and transport are lowered with acute exercise, the primary control of MGU shifts to that of glucose phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Distributed control of glucose uptake by working muscles of conscious mice: roles of transport and phosphorylation

Fueger

Bracy

Malabanan

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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; 10.1152/ ajpendo.00309.2003.-Muscle glucose uptake (MGU) is determined by glucose delivery, transport, and phosphorylation. C57Bl/6J mice overexpressing GLUT4, hexokinase II (HK II), or both were used to determine the barriers to MGU. A carotid artery and jugular vein were catheterized for arterial blood sampling and venous infusions. Experiments were conducted in conscious mice ϳ7 days after surgery. 2-Deoxy-[3 H]glucose was administered during rest or treadmill exercise to calculate glucose concentration-dependent (R g) and -independent (K g) indexes of MGU. Compared with wild-type controls, GLUT4-overexpressing mice had lowered fasting glycemia (165 Ϯ 6 vs. 115 Ϯ 6 mg/dl) and increased R g by 230 and 166% in the gastrocnemius and superficial vastus lateralis (SVL) muscles under sedentary conditions. GLUT4 overexpression was not able to augment exercise-stimulated R g or Kg. Whereas HK II overexpression had no effect on fasting glycemia (170 Ϯ 6 mg/dl) or sedentary R g, it increased exercise-stimulated R g by 82, 60, and 169% in soleus, gastrocnemius, and SVL muscles, respectively. Combined GLUT4 and HK II overexpression lowered fasting glycemia (106 Ϯ 6 mg/dl), increased nonesterified fatty acids, and increased sedentary R g. Combined GLUT4 and HK II overexpression did not enhance exercisestimulated Rg compared with HK II-overexpressing mice because of the reduced glucose concentration. GLUT4 combined with HK II overexpression resulted in a marked increase in exercise-stimulated K g. In conclusion, control of MGU shifts from membrane transport at rest to phosphorylation during exercise. Glucose transport is not normally a significant barrier during exercise. However, when the phosphorylation barrier is lowered by HK II overexpression, glucose transport becomes a key site of control for regulating MGU during exercise.delivery; glucose transporter 4; hexokinase; exercise; 2-deoxyglucose THE CONTROL OF skeletal muscle glucose uptake (MGU) is distributed over the following three serial steps: delivery of glucose from the blood to the sarcolemma, transport across the sarcolemmal membrane, and intracellular phosphorylation by hexokinase (HK; see Ref. 42). Both blood flow and capillary recruitment are important determinants of glucose delivery. Glucose transport is mediated by the facilitated diffusion of glucose through a GLUT family member. Under basal and sedentary conditions, GLUT1 facilitates much of the transport into skeletal muscle (10,30,38); however, after stimulation by contractions (3,8,37), GLUT4 translocates from an intracellular pool to the cell surface, thereby increasing the permeability of the sarcolemma to glucose. Whether HK activity or localization and hence the functional rate of glucose phosphorylation to glucose 6-phosphate (G-6-P) changes during acute stimulation by exercise remains to be clearly determined. While one step may exert dominance in controlling MGU under one condition, the primary control step may shift with physiological stimuli (11)(12)(13)(14)34).During sedentary conditions...

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“…In contrast, arterial blood glucose remained constant in chow-fed WT mice but increased at the onset of exercise and reached a plateau by 15 min of the 30-min protocol in mice fed a high-fat diet with or without a partial HK II deletion, such that blood glucose was greater in these groups. During exercise, the massive hyperemia (23,24) and translocation of GLUT4 from the cytoplasm to sarcolemma (25)(26)(27) leads to a robust increase in MGU. The result of these two exercise-stimulated events is that glucose phosphorylation capacity becomes increasingly important in determining MGU (10,13,14,28).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation Barriers to Skeletal and Cardiac Muscle Glucose Uptakes in High-Fat–Fed Mice

et al. 2007

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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 ⅐ kg Ϫ1 ⅐ min Ϫ1 ) or exercise with chow or high-fat feeding. RESEARCH DESIGN AND METHODS-C57BL/6J mice with (HKϩ/Ϫ ) 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 ϭ 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 ϩ/Ϫ ). 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 ϳ25% with either high-fat feeding or partial HK II knockout alone but by Ͼ50% when the two were combined. Insulin-stimulated R g was modestly impaired by high-fat feeding and partial HK II knockout independently (ϳ15-20%) but markedly reduced by the two together (ϳ40 -50%). Exercise-stimulated R g was reduced by ϳ50% 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. Diabetes 56:2476-2484, 2007 T he importance of limitations in muscle glucose phosphorylation capacity in insulin resistance is a point of contention. In rodent muscle, glucose phosphorylation to glucose-6-phosphate is catalyzed primarily by the hexokinase (HK) II isozyme. HK II content may be normal (1) or reduced (2) in insulinresistant states, depending on the muscle fiber type composition. Regardless, glucose phosphorylation capacity is affected due to allosteric inhibition of HK II by acyl-CoA and glucose-6-phosphate or compartmentation of HK II, its allosteric regulators, and its substrates (i.e., glucose and ATP). Insulin stimulation and exercise can be used to expose functional deficits in glucose phosphorylation capacity that may otherwise be undetectable (3). Indeed, we previously used such a strategy in conscious mice overexpressing HK II to provide evidence that glucose phosphorylation is, in fact, impaired by high-fat feeding (4). Th...

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Vascular recruitment in forearm muscles during exercise

Cited by 12 publications

References 7 publications

Control of Exercise-stimulated Muscle Glucose Uptake by GLUT4 Is Dependent on Glucose Phosphorylation Capacity in the Conscious Mouse

Control of Exercise-stimulated Muscle Glucose Uptake by GLUT4 Is Dependent on Glucose Phosphorylation Capacity in the Conscious Mouse

Distributed control of glucose uptake by working muscles of conscious mice: roles of transport and phosphorylation

Phosphorylation Barriers to Skeletal and Cardiac Muscle Glucose Uptakes in High-Fat–Fed Mice

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