Fiber type-specific expression of GLUT4 in human skeletal muscle: influence of exercise training.

The fiber type-specific expression of skeletal muscle GLUT4 and the effect of 2 weeks of low-intensity training were investigated in 8 young untrained male subjects. Single muscle fibers were dissected from a vastus lateralis biopsy sample. Based on myosin heavy chain (MHC) expression, fibers were pooled into 3 groups (MHC I, MHC IIA, and MHC IIX), and the GLUT4 content of 15-40 pooled fibers was determined using SDS-PAGE and immunological detection. The GLUT4 content in pooled muscle fibers expressing MHC I was approximately 20% higher (P < 0.05) than that in muscle fibers expressing MHC IIA or MHC IIX. No difference in GLUT4 could be detected between fibers expressing MHC IIA or MHC IIX. Two weeks of exercise training increased (P < 0.05) the peak power output of the knee extensors by 13%, the maximal activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase by 21 and 18%, respectively, and the GLUT4 protein content by 26% in a muscle homogenate. Furthermore, a 23% increase (P < 0.05) in GLUT4 was seen in fibers expressing the MHC I isoform after exercise training for 2 weeks. No change was seen in fibers expressing MHC IIA or MHC IIX. In conclusion, our data directly demonstrate that GLUT4 is expressed in a fiber type-specific manner in human skeletal muscle, although fiber type differences are relatively small. In addition, low-intensity exercise training recruiting primarily fibers expressing MHC I increased GLUT4 content in these fibers but not in fibers expressing MHC IIA or MHC IIX, indicating that GLUT4 protein content is related more to activity level of the fiber than to its fiber type, which is defined by expression of contractile protein.

Exercise diminishes the activity of acetyl-CoA carboxylase in human muscle.

Studies in rats suggest that increases in fatty acid oxidation in skeletal muscle during exercise are related to the phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), and secondary to this, a decrease in the concentration of malonyl-CoA. Studies in human muscle have not revealed a consistent decrease in the concentration of malonyl-CoA during exercise; however, measurements of ACC activity have not been reported. Thus, whether the same mechanism operates in human muscle in response to physical activity remains uncertain. To investigate this question, ACC was immunoprecipitated from muscle of human volunteers and its activity assayed in the same individual at rest and after one-legged knee-extensor exercise at 60, 85, and 100% of knee extensor VO2max. ACC activity was diminished by 50-75% during exercise with the magnitude of the decrease generally paralleling exercise intensity. Treatment of the immunoprecipitated enzyme with protein phosphatase 2A restored activity to resting values, suggesting the decrease in activity was due to phosphorylation. The measurement of malonyl-CoA in the muscles revealed that its concentration is 1/10 of that in rats, and that it is diminished (12-17%) during the higher-intensity exercises. The respiratory exchange ratio increased with increasing exercise intensity from 0.84 +/- 0.02 at 60% to 0.99 0.04 at 100% VO2max. Calculated rates of whole-body fatty acid oxidation were 121 mg/min at rest and 258 +/- 35, 264 +/- 63, and 174 +/- 76 mg/min at 60, 85, and 100% VO2max, respectively. The results show that ACC activity, and to a lesser extent malonyl-CoA concentration, in human skeletal muscle decrease during exercise. Although these changes may contribute to the increases in fat oxidation from rest to exercise, they do not appear to explain the shift from mixed fuel to predominantly carbohydrate utilization when exercise intensity is increased.

Muscle fiber characteristics in postmenopausal women with normal or impaired glucose tolerance.

OBJECTIVE: Muscle fiber characteristics are altered in type 2 diabetes. We studied whether these alterations also exist in impaired glucose tolerance (IGT) and whether they are determinants of insulin sensitivity and glucose tolerance in postmenopausal women. RESEARCH DESIGN AND METHODS: Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from 77 postmenopausal women aged 57-59 years: 50 women with normal glucose tolerance (NGT) and 27 with IGT. The IGT group had a reduced insulin sensitivity compared with the NGT group (euglycemic-hyperinsulinemic clamp) (P = 0.003). RESULTS: The groups did not differ in muscle fiber composition, as judged by the percentage of type I, IIa, or IIx fibers. In contrast, the IGT group had increased size of the IIa (mean +/-SD 3,776+/-987 vs. 3,078+/-862 microm2, P = 0.002) and IIx fibers (2,730+/-1,037 vs. 2,253+/-672 microm2, P = 0.017). There was a trend for the capillary diffusion areas (the muscle area supplied by each capillary) to be larger in the IGT group for the IIa (1,132+/-286 vs. 1,013+/-240 microm2, P = 0.061) and IIx fibers (1,020+/-246 vs. 906+/-240 microm2, P = 0.058). In the entire group, insulin sensitivity correlated with the size of the type IIa fibers (r = -0.28, P = 0.013), but not with the percentages of muscle fiber types. In a multiple regression, insulin sensitivity was determined by body fat content and HDL cholesterol level, while the size of the IIa fibers was not included in the model. Glucose tolerance was independently predicted by the number of capillaries/type I fiber, as well as by insulin sensitivity and triglyceride levels. CONCLUSIONS: We conclude that although muscle fiber composition is not altered, women with IGT have larger type IIa and IIx muscle fibers and a trend for increased capillary diffusion areas for these fibers, compared with women with NGT. In the entire group, insulin sensitivity was determined mainly by body fat content, while muscle fiber capillarization may be of importance for glucose tolerance.

Insulin action in growth hormone-deficient and age-matched control rats: effect of growth hormone treatment.

The isolated effect of growth hormone on carbohydrate metabolism in rat skeletal muscle was studied in growth hormone-deficient dwarf rats (dw/dw) treated with either recombinant human growth hormone or saline for 10 days. In addition, age-matched heterozygous (DW/dw) (normal weight and plasma IGF-I) control rats were treated with saline. Growth hormone increased weight gain from 0.1+/-0.1 (s.e.m) to 3.6+/-0.1 g/day and plasma IGF-I concentration from 364+/-23 to 451+/-32 ng/ml. Glucose metabolism in skeletal muscle perfused with basal, submaximal and maximal concentrations (0, 600 and 60 000 pmol/l respectively) of insulin was not changed by growth hormone. No change could be detected in the total number of glucose transporters (GLUT1 and GLUT4) in the skeletal muscles, except from a lower amount of GLUT4 in the soleus muscle in the heterozygous control group. However, at submaximal insulin concentrations, skeletal muscle glucose uptake and transport were significantly lower in the heterozygous control group compared with the growth hormone-deficient group. This could indicate either a direct long-term effect of growth hormone or more likely a secondary effect attributable to the difference in body weight (205.2+/-3.1 vs 361. 6+/-5.9 g for dwarf rats and heterozygous controls respectively), and thereby muscle fibre size, between the groups probably resulting in lower average interstitial insulin and glucose concentrations at a given plasma concentration in the heterozygous rats. It is concluded that restoration of subnormal growth hormone concentrations for 10 days has no effect on insulin-stimulated glucose metabolism in skeletal muscle in vitro.

Effect of 6 months of GH treatment on myosin heavy chain composition in GH-deficient patients.

OBJECTIVE: To investigate the effect of GH on myosin heavy chain (MHC) isoform composition, physical fitness and body composition in GH-deficient (GHD) patients. DESIGN: Twenty-two GHD patients were randomized in a double blind manner and half were treated with recombinant human GH (rhGH) and half were treated with placebo for 6 months. Twelve age-matched controls were also included in the study. METHODS: MHC isoform composition in biopsies obtained from the vastus lateralis muscle was determined using SDS-PAGE. Physical fitness was determined on a bicycle ergometer and body composition was determined using bioelectrical impedance analysis. RESULTS: More MHC IIX (28.9 +/- 4.1% and 10.0 +/- 3.1% in GHD and controls respectively (means +/- S.E.M.)) and less MHC I (36.2 +/- 2.4% and 51.7 +/- 3.9% in GHD and controls respectively (means +/- S.E.M.)) were present in the GHD patients compared with the controls. No significant difference in the amount of MHC IIA was detected. Linear regression was used to determine the relationship between variables. There were no significant relationships between the concentration of insulin-like growth factor-I (IGF-I) or the body composition and the MHC composition. Maximal oxygen uptake (VO(2)max) per kg body weight (BW) (litres/min per kg) correlated significantly with the amount of MHC I (r=0.60) and MHC IIX (r=-0.72) but not with the amount of MHC IIA (r=0.35). Treatment of GHD patients with rhGH for 6 months increased the concentration of IGF-I, lean body mass and decreased fat mass but had no effect on MHC composition and physical fitness. CONCLUSIONS: We conclude that a major part of the differences in MHC composition between GHD patients and age-matched controls can be explained by variation in physical fitness. The severity of the GHD and the body composition does not seem to be important for the MHC composition. Furthermore, treatment with GH for 6 months does not affect MHC composition in GHD patients.

Muscle glycogen accumulation after a marathon: roles of fiber type and pro- and macroglycogen.

Muscle glycogen remains subnormal several days after muscle damaging exercise. The aims of this study were to investigate how muscle acid-soluble macroglycogen (MG) and acid-insoluble proglycogen (PG) pools are restored after a competitive marathon and also to determine whether glycogen accumulates differently in the various muscle fiber types. Six well-trained marathon runners participated in the study, and muscle biopsies were obtained from the vastus lateralis of the quadriceps muscle before, immediately after, and 1, 2, and 7 days (days 1, 2, and 7, respectively) after the marathon. During the race, 56 +/- 3.8% of muscle glycogen was utilized, and a greater fraction of MG (72 +/- 3.7%) was utilized compared with PG (34 +/- 6.5%). On day 2, muscle glycogen and MG values remained lower than prerace values, despite a carbohydrate-rich diet, but they had both returned to prerace levels on day 7. The PG concentration was lower on day 1 compared with before the race, whereas there were no significant differences between the prerace PG concentration and the concentrations on days 2 and 7. On day 2 the glycogen concentration was particularly low in the type I fibers, indicating that local processes are important for the accumulation pattern. We conclude that a greater fraction of human muscle MG than of PG is utilized during a marathon and that accumulation of MG is particularly delayed after the prolonged exercise bout. Furthermore, factors produced locally appear important for the glycogen accumulation pattern.

Effect of eccentric exercise on natural killer cell activity.

The effect of eccentric one-legged exercise on natural killer (NK) cell activity was studied in eight healthy males. To distinguish between local and systemic effects, blood samples were collected from veins in the exercising leg and resting arm. However, the results did not significantly differ between the leg and arm. To eliminate diurnal variations, the results were compared with a control group that did not exercise but had blood samples collected at the same time points. In the exercising group, plasma creatine kinase increased progressively during and up to 4 days after exercise. The percentage of CD16+ NK cells increased during exercise, which was paralleled by an increase in the NK cell activity per fixed number of blood mononuclear cells. The NK cell activity on a per NK cell basis did not change. The percentage of CD3+, CD4+, CD8+, CD19+, and CD14+ cells did not change significantly during exercise. The present study thus showed that eccentric exercise with a relatively small muscle mass (1 quadriceps femoris muscle) causes systemic effects on NK cells. It is suggested that the increase in plasma epinephrine during eccentric exercise is responsible for the observed increase in the percentage of CD16+ cells.

Training affects muscle phospholipid fatty acid composition in humans.

Training improves insulin sensitivity, which in turn may affect performance by modulation of fuel availability. Insulin action, in turn, has been linked to specific patterns of muscle structural lipids in skeletal muscle. This study investigated whether regular exercise training exerts an effect on the muscle membrane phospholipid fatty acid composition in humans. Seven male subjects performed endurance training of the knee extensors of one leg for 4 wk. The other leg served as a control. Before, after 4 days, and after 4 wk, muscle biopsies were obtained from the vastus lateralis. After 4 wk, the phospholipid fatty acid contents of oleic acid 18:1(n-9) and docosahexaenoic acid 22:6(n-3) were significantly higher in the trained (10.9 +/- 0.5% and 3.2 +/- 0.4% of total fatty acids, respectively) than the untrained leg (8.8 +/- 0.5% and 2.6 +/- 0.4%, P < 0.05). The ratio between n-6 and n-3 fatty acids was significantly lower in the trained (11.1 +/- 0.9) than the untrained leg (13.1 +/- 1.2, P < 0.05). In contrast, training did not affect muscle triacylglycerol fatty acid composition. Citrate synthase activity was increased by 17% in the trained compared with the untrained leg (P < 0.05). In this model, diet plays a minimal role, as the influence of dietary intake is similar on both legs. Regular exercise training per se influences the phospholipid fatty acid composition of muscle membranes but has no effect on the composition of fatty acids stored in triacylglycerols within the muscle.

Training effects on muscle glucose transport during exercise.

Muscle glucose uptake is increased during exercise compared to rest. In general, muscle glucose uptake increases with increasing exercise intensity and duration. Whereas the arterio-venous concentration difference only increases 2-4-fold during exercise compared with rest the increase in muscle perfusion in 10-20 times and therefore quantitatively very important. During exercise the surface membrane glucose transport capacity increases in skeletal muscle primarily due to an increase in surface membrane GLUT4 protein content. Endurance training decreases muscle glucose uptake during exercise at a given absolute submaximal work-load despite a large increase in muscle GLUT4 protein content. We have shown that this decrease in glucose uptake at least in part is due to a blunted exercise-induced increase in sarcolemmal glucose transport capacity secondary to a blunted increase in sarcolemmal GLUT4 transporter number. Thus, endurance training leads to a marked reduction of the fraction of muscle GLUT4 that is translocated during a given submaximal exercise bout. Whether this is true also during exercise at higher intensities remains to be seen.

Low-intensity training dissociates metabolic from aerobic fitness.

This study investigated the effect of prolonged whole-body low-intensity exercise on blood lipids, skeletal muscle adaptations and aerobic fitness. Seven male subjects completed a 32-day crossing of the Greenland icecap on cross-country skies and before and after this arm or leg cranking was performed on two separate days and biopsies were obtained from arm and leg muscle, and venous blood was sampled. During the crossing, subjects skied for 342+/-42 min/day and body mass was decreased by 7.1+/-0.7 kg. Peak leg oxygen uptake (4.6+/-0.2 L/min) was decreased (P<0.05) by 7% whereas peak arm oxygen uptake (3.0+/-0.2 L/min) remained unchanged. Total and low-density lipoprotein cholesterol (5.0+/-0.2 and 3.20.2 mmol/L) were decreased by 8% and 20%, respectively. Muscle beta-hydroxy-acyl-CoA dehydrogenase activity was increased with 22% in arm (P=0.08) and remained unchanged in leg muscle. Hormone sensitive lipase activity was similar in arm and leg muscle prior to the expedition and was not significantly affected by the crossing. In conclusion, an improved blood lipid profile and thus metabolic fitness was present after prolonged low-intensity training and this occurred in spite of a decreased aerobic fitness and an unchanged arm and leg muscle hormone-sensitive lipase activity.

Four weeks one-leg training and high fat diet does not alter PPARalpha protein or mRNA expression in human skeletal muscle.

UNLABELLED: Fatty acid metabolism is influenced by training and diet with exercise training mediating this through activation of nuclear hormone receptor peroxisome proliferator-activated receptor alpha (PPARalpha) in skeletal muscle. This study investigated the effect of training and high fat or normal diet on PPARalpha expression in human skeletal muscle. Thirteen men trained one leg (T) four weeks (31.5 h in total), while the other leg (UT) served as control. During the 4 weeks six subjects consumed high fat (FAT) diet and seven subjects maintained a normal (CHO) diet. Biopsies were obtained from vastus lateralis muscle in both legs before and after training. After the biopsy, one-leg extension exercise was performed in random order with both legs 30 min at 95% of workload max. A training effect was evident as citrate synthase activity increased (P < 0.05) by 15% in the trained, but not the control leg in both groups. During exercise respiratory exchange ratio was lower in FAT (0.86 +/- 0.01, 0.83 +/- 0.01, mean +/- SEM) than CHO (0.96 +/- 0.02, 0.94 +/- 0.03) and in UT than T legs, respectively. The PPARalpha protein (144 +/- 44, 104 +/- 28, 79 +/- 15, 79 +/- 14, % of pre level) and PPARalpha mRNA (69 +/- [2, 2], 78 +/- [7, 6], 92 +/- [22, 18], 106 +/- [21, 18], % of pre level, geometric mean +/- SEM) expression remained unchanged by diet and training in FAT (UT, T) and CHO (UT, T), respectively. After the training and diet CS, HAD, PPARalpha, UCP2, UCP3 and mFABP mRNA content remained unchanged, whereas GLUT4 mRNA was lower in both groups and LDHA mRNA was lower (P < 0.05) only in FAT. IN CONCLUSION: 4 weeks one leg knee extensor training did not affect PPARalpha protein or mRNA expression. Furthermore, higher fat oxidation during exercise after fat rich diet was not accompanied by an increased PPARalpha protein or mRNA expression after 4 weeks.

Relationship between muscle fibre composition, glucose transporter protein 4 and exercise training: possible consequences in non-insulin-dependent diabetes mellitus.

Skeletal muscle is composed of different fibre types, which differ in contractile as well as in metabolic properties. The myosin molecule, which exists in several different isoforms, is of major importance in determining the contractile properties of the muscle cell. The plasticity of skeletal muscle is reflected in this tissue's adaptability to changes in the functional demand. In both rats and humans, a decrease in activity level will in most cases change the muscle fibre composition towards faster myosin isoforms and an increase in activity level (such as seen with exercise training) will induce an increase in slower myosin isoforms. The glucose transporter protein 4 (GLUT4), which is the major insulin regulatable glucose transporter in mammalian skeletal muscle, is found in larger amounts in slow muscle fibres compared with fast muscle fibres. An increase in activity level will increase the GLUT4 protein expression and a decrease in activity level will in most cases decrease GLUT4. Thus, there seems to be some kind of relationship between the muscle fibre type and GLUT4. However, the main factor regulating both the GLUT4 protein expression and the muscle fibre composition seems to be the activity level of the muscle fibre. Patients suffering from non-insulin-dependent diabetes mellitus (NIDDM) are insulin resistant in their skeletal muscles but are generally normal when it comes to skeletal muscle fibre composition and the GLUT4 protein expression. There is good evidence that exercise training beneficially impacts on insulin sensitivity in healthy individuals and in patients with type II diabetes. An increase in the GLUT4 protein expression in skeletal muscle may at least partly explain this effect of training.

Eccentric exercise decreases glucose transporter GLUT4 protein in human skeletal muscle.

1. Eccentric exercise causes impaired postexercise glycogen resynthesis. To study whether changes in muscle concentration of the glucose transporter (GLUT4) protein might be involved, seven healthy young men performed one-legged eccentric exercise by resisting knee flexion enforced by a motor-driven device. 2. The GLUT4 protein concentration in the exercised and in the control thigh was unchanged immediately after exercise. On days 1 and 2 after exercise, the GLUT4 protein concentration in the exercised muscle was 68 +/- 10 and 64 +/- 10% (means +/- S.E.M.; P < 0.05), respectively, of the concentration in the control muscle, and had returned to control values on days 4 and 7. 3. The muscle glycogen concentration decreased from 404 +/- 44 to 336 +/- 44 mmol (kg dry wt)-1 (P < 0.05) during exercise. The glycogen concentration remained significantly lower than in the control thigh on days 1 and 2 after exercise but on days 4 and 7 no differences were found. 4. Although no cause-effect relationship was established, these findings may suggest that decreased muscle concentrations of GLUT4 protein, and, hence, a decreased rate of glucose transport into muscle cells, may be involved in the sustained low glycogen concentration seen after eccentric exercise.

Growth hormone induces muscle fibre type transformation in growth hormone-deficient rats.

The effect of recombinant human growth hormone (rhGH) on growth and composition of muscle was studied in growth hormone-deficient rats (dw/dw) treated for 10 days with either rhGH (GH) or with placebo (PLA). Age-matched control rats (DW/dw) (AGE) were treated as PLA. Growth rate increased (P < 0.05) when rats were treated with rhGH and plasma insulin-like growth factor-1 concentration was higher (P < 0.05) in GH and AGE than in PLA. The wet weight of the soleus (SOL) and the extensor digitorum longus muscles (EDL) was less in PLA compared to GH and AGE (P < 0.05). In the SOL, the amount of myosin heavy chain (MHC) I was lower (69.1 +/- 1.7%) (Mean +/- SEM) in PLA compared to both GH (85.3 +/- 2.3%) and AGE (76.4 +/- 1.6%) (P < 0.05). At the same time the amount of MHC IIA/IIX was higher (30.9 +/- 2.2%) in PLA compared to GH (14.7 +/- 2.3%) and AGE (23.6 +/- 1.6% (P < 0.05)). In EDL, treatment with rhGH did not significantly affect MHC-isoforms or the fibre type composition, but 11% more MHC IIB and 11% less MHC IIA/IIX was observed in PLA compared to AGE (P < 0.05) suggesting a long-term effect of growth hormone. MHC-isoform data were confirmed using histochemistry. In addition, in the SOL, the maximal activity of 3-hydroxyacyl-CoA dehydrogenase (HAD) in GH and AGE was higher (22 and 27%, respectively) than in PLA (P < 0.05). In the EDL, no differences were observed in maximal activity of HAD. In conclusion, the data support a role for growth hormone in muscle fibre growth and differentiation.

Exercise metabolism in human skeletal muscle exposed to prior eccentric exercise.

1. The effects of unaccustomed eccentric exercise on exercise metabolism during a subsequent bout of graded concentric exercise were investigated in seven healthy male subjects. Arterial and bilateral femoral venous catheters were inserted 2 days after eccentric exercise of one thigh (eccentric thigh) and blood samples were taken before and during graded two-legged concentric knee-extensor exercise. Muscle biopsies were obtained from the eccentric and control vastus lateralis before (rest) and after (post) the concentric exercise bout. 2. Maximal knee-extensor concentric exercise capacity was decreased by an average of 23 % (P < 0.05) in the eccentric compared with the control thigh. 3. The resting muscle glycogen content was lower in the eccentric thigh than in the control thigh (402 +/- 30 mmol (kg dry wt)-1 vs. 515 +/- 26 mmol (kg dry wt)-1, means +/- s.e.m., P < 0.05), and following the two-legged concentric exercise this difference substantially increased (190 +/- 46 mmol (kg dry wt)-1 vs. 379 +/- 58 mmol (kg dry wt)-1, P < 0.05) despite identical power and duration of exercise with the two thighs. 4. There was no measurable difference in glucose uptake between the eccentric and control thigh before or during the graded two-legged concentric exercise. Lactate release was higher from the eccentric thigh at rest and, just before termination of the exercise bout, release of lactate decreased from this thigh (suggesting decreased glycogenolysis), whereas no decrease was found from the contralateral control thigh. Lower glycerol release from the eccentric thigh during the first, lighter part of the exercise (P < 0.05) suggested impaired triacylglycerol breakdown. 5. At rest, sarcolemmal GLUT4 glucose transporter content and glucose transport were similar in the two thighs, and concentric exercise increased sarcolemmal GLUT4 content and glucose transport capacity similarly in the two thighs. 6. It is concluded that in muscle exposed to prior eccentric contractions, exercise at a given power output requires a higher relative workload than in undamaged muscle. This increases utilization of the decreased muscle glycogen stores, contributing to decreased endurance.

Eccentric exercise decreases maximal insulin action in humans: muscle and systemic effects.

1. Unaccustomed eccentric exercise decreases whole-body insulin action in humans. To study the effects of one-legged eccentric exercise on insulin action in muscle and systemically, the euglycaemic clamp technique combined with arterial and bilateral femoral venous catheterization was used. Seven subjects participated in two euglycaemic clamps, performed in random order. One clamp was preceded 2 days earlier by one-legged eccentric exercise (post-eccentric exercise clamp (PEC)) and one was without the prior exercise (control clamp (CC)). 2. During PEC the maximal insulin-stimulated glucose uptake over the eccentric thigh was marginally lower when compared with the control thigh, (11.9%, 64.6 +/- 10.3 vs. 73.3 +/- 10.2 mumol kg-1 min-1, P = 0.08), whereas no inter-thigh difference was observed at a submaximal insulin concentration. The glycogen concentration was lower in the eccentric thigh for all three clamp steps used (P < 0.05). The glucose transporter GLUT4 protein content was on average 39% lower (P < 0.05) in the eccentric thigh in the basal state, whereas the maximal activity of glycogen synthase was identical in the two thighs for all clamp steps. 3. The glucose infusion rate (GIR) necessary to maintain euglycaemia during maximal insulin stimulation was lower during PEC compared with CC (15.7%, 81.3 +/- 3.2 vs. 96.4 +/- 8.8 mumol kg-1 min-1, P < 0.05). 4. Our data show that 2 days after unaccustomed eccentric exercise, muscle and whole-body insulin action is impaired at maximal but not submaximal concentrations. The local effect cannot account for the whole-body effect, suggesting the release of a factor which decreases insulin responsiveness systemically.

Regulation of muscle glucose transport during exercise.

In the present short review some factors affecting glucose utilization during exercise in skeletal muscle will be briefly described. Special focus will be put on the glucose transport step across the sarcolemma. Glucose transporters (GLUT4) are expressed at a surprisingly similar level in the different muscle fiber types in human skeletal muscle in contrast to findings in the rat. When working at the same absolute work load muscle glucose transport is decreased in trained compared with untrained muscle in part due to a decrease in GLUT4 translocation to the sarcolemma in trained muscle. However, when trained and untrained muscle are stressed severely by a workload taxing 100% of their peak oxygen uptake in a glycogen-depleted state, then glucose uptake is larger in trained than in untrained muscle and correlates with muscle GLUT4 content. Finally, the possible role of the AMP-activated protein kinase (AMPK) in regulating glucose uptake during exercise is discussed. It is indicated that at present no experiments definitively link activation of AMPK to activation of muscle glucose transport during exercise.