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H Galbo

Publications and source records attributed to H Galbo.

At least 55 records · Page 3Linked to original sources
PubMed1998

Molecular mechanisms involved in GLUT4 translocation in muscle during insulin and contraction stimulation.

Studies in mammalian cells have established the existence of numerous intracellular signaling cascades that are critical intermediates in the regulation of various biological functions. Over the past few years considerable research has shown that many of these signaling proteins are expressed in skeletal muscle. However, the detailed mechanisms involved in the regulation of glucose transporter (GLUT4) translocation from intracellular compartments to the cell surface membrane in response to insulin and contractions in skeletal muscle are not well understood. In the present essay we report three different approaches to unravel the GLUT4 translocation mechanism: 1. specific pertubation of the insulin and/or contraction signaling pathways; 2. characterization of the protein composition of GLUT4-containing vesicles with the expectation that knowledge of the constituent proteins of the vesicles may help in understanding their trafficking; 3. degree of co-immunolocalization of the GLUT4 glucose transporters with other membrane marker proteins assessed by immunofluorescense and electron microscopy.

Animals↗
PubMed1998

Somatostatin attenuates the hyperthermia induced increase in neutrophil concentration.

This study was designed to test the hypothesis that the immune changes seen during in vivo whole body hyperthermia are mediated by elevations in the plasma concentrations of either catecholamines, growth hormone or beta-endorphins. Eight healthy volunteers were immersed in a hot water bath (WI; water temperature 39.5 degrees C) for 2 h during which their rectal temperature rose to 39.5 degrees C. In a single blind, randomized, cross-over study the stress hormone effects were blocked one at a time by administration of propranolol, somatostatin or naloxone; the results were compared to those obtained during saline infusion (control). Blood samples were collected before, at the end of 2 h of WI (body temperature 39.5 degrees C), and 2 h later. Hormone blockade did not abolish the hyperthermia-induced recruitment of natural killer (NK) cells to the blood, and no influence was observed on the percentages or concentrations of any other subpopulations of blood mononuclear cells, except that the number of cluster designation (CD)3+ cells slightly increased after hyperthermia only in the propranolol experiment. Furthermore, the NK cell activity, both unstimulated and interferon-alpha or interleukin-2 stimulated, did not differ from the control situation. It is of interest, however, that somatostatin partly abolished the hyperthermia induced increase in the neutrophil number. Based on these data and previous results showing that growth hormone infusion increases the concentration of neutrophils in the blood, it is suggested that growth hormone is at least partly responsible for hyperthermia induced neutrocytosis.

Adult↗
PubMed1998

Effects of elevated plasma noradrenaline concentration on the immune system in humans.

This study was designed to test the hypothesis that elevated plasma noradrenaline concentrations contribute to the exercise-induced modulation of the activity and percentage of the natural killer (NK) cells, and the leucocyte concentration. In a single blind, controlled, cross-over study, eight healthy men had noradrenaline infused for 1 h and achieved plasma noradrenaline concentrations comparable (20-fold increment) to those previously observed in cycle ergometer exercise (75% of maximal oxygen uptake for 1 h). The noradrenaline infusion increased the unstimulated, the interleukin-2 and interferon-alpha stimulated NK cell activity, and the percentage of CD16+ cells. The natural lytic activity per CD16+ cell however, did not change. The concentration of neutrophils, lymphocytes and CD16+ cells increased during the infusion. The neutrophil concentration remained elevated 2 h after infusion, at which time the lymphocyte count was back to normal. These results are comparable with the effects in the exercise model, and it is suggested that the augmented plasma noradrenaline concentrations, seen during extreme exercise, may participate in the exercise-induced immune changes.

Adrenergic alpha-Agonists↗
PubMed1998

The natural killer cell response to exercise in spinal cord injured individuals.

In order to evaluate exercise-induced changes in natural killer (NK) and other immunocompetent cells in spinal cord injured individuals, immunological competent blood cells and stress hormones were followed in five paraplegic and six quadriplegic subjects in relation to 30 min electrically stimulated cycling exercise. The leukocyte and lymphocyte concentrations increased during exercise. In the recovery period, the concentration of neutrophils increased, whereas the lymphocytes decreased. The percentage and concentration of NK cells increased during exercise in the paraplegic group and returned to pre-exercise level 2 h after, whereas no changes were seen in these measures for the quadriplegic group. No changes in activated CD38+ NK cells appeared. Unstimulated and interferon-alpha or interleukin-2 stimulated NK cell activity increased during exercise and returned to pre-exercise level 2 h after with no distinction between paraplegics and quadriplegics. The concentrations of plasma growth hormone and catecholamines increased during exercise, with the rise in epinephrine being more pronounced in paraplegic than in quadriplegic subjects, indicating a difference between the groups in sympathetic nervous system integrity. The sympathoadrenal activity is concluded to be responsible for recruitment of NK cells to the blood during exercise.

Adult↗
PubMed1998

The value of ultrasonography in the diagnosis of labral lesions in patients with anterior shoulder dislocation.

OBJECTIVE: To evaluate the ability of ultrasonography to detect labral lesions in patients with anterior shoulder dislocation. METHODS: We examined 29 patients with anterior shoulder dislocation with ultrasonography prior to arthroscopy. RESULTS: Twenty-six patients had labral lesions diagnosed by arthroscopy. These lesions were detected by ultrasonography with a sensitivity of 88% and a specificity of 67%. All lesions affected the anterior labrum, while six extended to the posterior labrum. The latter were not visualized by ultrasonography. CONCLUSION: Ultrasonography is valuable in the detection of anterior labral lesions even in patients with recent shoulder dislocation.

Adolescent↗
PubMed1998

Post-mortem ultrasonographic assessment of the anterior glenoid labrum.

OBJECTIVE: The purpose of this study was to investigate the identification of the anterior glenoid labrum with ultrasonography. METHODS: Twelve cadaveric shoulders from subjects 74 to 85 years of age were examined by ultrasonography. Under ultrasonographic guidance, a small amount of dye was injected on the structure believed to be the anterior glenoid labrum, whereafter the shoulders were dissected. RESULTS: In 11 shoulders the dye was found in close relation to the glenoid labrum. Comparing the labrum to a watch face numbered clockwise in the left shoulder, and counter clockwise in the right, the part seen was located between 1 and 5 o'clock. Signs of degeneration were found in six labra by ultrasonography and verified by blindfolded dissection. CONCLUSIONS: Ultrasonography can identify the anterior glenoid labrum and distinguish degenerated from normal labra.

Aged↗
PubMed1998

Immunological effects of a hyperinsulinaemic euglycaemic insulin clamp in healthy males.

The purpose of this study was to determine the in-vivo and in-vitro effects of insulin, at physiological and supraphysiological concentrations, on the human immune system. Ten healthy young men went through a sequential two-step hyperinsulinaemic euglycaemic clamp. Plasma insulin concentrations were increased from baseline (9.0 microU/ml) to 49.1 microU/ml after 1 h of insulin infusion (step I) and to 1281 microU/ml (step II) after 2 h of infusion. As control experiments infusions of isotonic saline were performed. The unstimulated natural killer (NK) cell activity among blood mononuclear cells (BMNC) increased in response to supraphysiological plasma insulin levels (baseline versus step II: 20.6 +/- 11.3 versus 27.8 +/- 14.4%). The percentages of the D16+ NK cells did not change, indicating an enhanced cytotoxic capability per individual NK cell. Insulin also slightly increased the activity of NK cells in vitro. A decline at step II in the concentrations of monocytes (0.29 +/- 0.09 versus 0.12 +/- 0.03 x 10(9)/L), lymphocytes (1.57 +/- 0.46 versus 1.22 +/- 0.25 x 10(9)/L), and CD16+(24.2 +/- 17.5 versus 16.7 +/- 11.2 x 10(7)/L), CD14+ (20.9 +/- 10.8 versus 8.6 +/- 3.9 x 10(7)/L), HLA-DR+ (37.2 +/- 22.1 versus 19.2 +/- 10.7 x 10(7)/L) and CD45RO+ (91.6 +/- 33.4 versus 61.7 +/- 6.4 x 10(7)/L) cells as well as in the percentages of CD14+ cells (11.2 +/- 4.7 versus 6.4 +/- 2.3%) and CD14+/HLA-DR+ monocytes (9.7 +/- 3.9 versus 4.8 +/- 2.8%) were observed. No changes were found at step I. Hyperinsulinaemia did not change the percentages of the CD3+, CD4+, CD8+, CD19+, CD56+, CD11a+, CD45RO+ and CD45RA+ cells, the numbers of circulating immunoglobulin (Ig)G-, IgA- and IgM- secreting cells, or the proliferative responses of BMNC to phytohaemagglutinin, purified derivative of tuberculin or interleukin (IL)-2. Hyperinsulinaemia did not change the in-vitro sensibility to insulin. In conclusion, supraphysiological insulin levels increased the activity of the individual NK cells, but decreased the numbers of NK cells, lymphocytes and activated monocytes. The findings are presumably of minor clinical relevance but may indicate an insulin-induced immune activation.

Adult↗
PubMed1998

Lactate production and clearance in exercise. Effects of training. A mini-review.

Lactate accumulates if pyruvate formation exceeds pyruvate oxidation. Accelerated glycogenolysis is essential for lactate production. Glycogen and epinephrine enhance glycogen phosphorylase activity and this is higher in type II b than in type I fibers. Pyruvate oxidation is enhanced by exercise-induced increase in pyruvate dehydrogenase activity and is relatively impaired by low oxygen availability and low mitochondrial oxidative capacity. During exercise lactate is eliminated in liver, heart, and resting and working muscle. In muscle, elimination depends on plasma concentration, fiber type, and fiber conditions. Due to influence on hormonal response, mitochondrial oxidative capacity and fiber recruitment, training diminishes glycogenolysis and lactate production. Training also increases lactate clearance. This reflects increased hepatic capacity for gluconeogenesis as well as increased lactate transport capacity and oxidative capacity and reduced glycogenolysis in muscle. The fact that endurance performance can be predicted from the plasma lactate versus exercise intensity relationship illustrates that the plasma lactate level is a finely balanced result of the interplay between many factors of importance for endurance exercise.

Anaerobiosis↗
PubMed1998

Influence of minor increases in plasma catecholamines on natural killer cell activity.

This study was designed to test the hypothesis that the modulations of the human immune system in relation to in vivo whole body hyperthermia may be ascribed to elevations in the plasma epinephrine and norepinephrine concentrations. In a single-blind, controlled, cross-over study, 8 healthy volunteers were selectively infused norepinephrine and epinephrine, respectively, for 1 h, in order to obtain twofold increases in the plasma concentrations of these hormones, thereby mimicking the increases seen during in vivo whole body hyperthermia. Epinephrine infusion increased baseline, interleukin-2 and interferon-alpha stimulated natural killer cell activity, and the percentage and concentration of cluster designation (CD)16+ cells, whereas the neutrophil and lymphocyte count or the CD3+, CD4+, CD8+, CD19+ and CD14+ cell subtypes were not influenced. Norepinephrine infusion did not cause any changes in these variables. It is concluded that epinephrine, but not norepinephrine, may be responsible for the hyperthermia-induced effects on natural killer cells.

Adult↗
PubMed1997

The effect of altitude hypoxia on glucose homeostasis in men.

1. Exposure to altitude hypoxia elicits changes in glucose homeostasis with increases in glucose and insulin concentrations within the first few days at altitude. Both increased and unchanged hepatic glucose production (HGP) have previously been reported in response to acute altitude hypoxia. Insulin action on glucose uptake has never been investigated during altitude hypoxia. 2. In eight healthy, sea level resident men (27 +/- 1 years (mean +/- S.E.M); weight, 72 +/- 2 kg; height, 182 +/- 2 cm) hyperinsulinaemic (50 mU min-1 m-2), euglycaemic clamps were carried out at sea level, and subsequently on days 2 and 7 after a rapid passive ascent to an altitude of 4559 m. 3. Acute mountain sickness scores increased in the first days of altitude exposure, with a peak on day 2. Basal HGP did not change with the transition from sea level (2.2 +/- 0.2 mg min-1 kg-1) to altitude (2.0 +/- 0.1 and 2.1 +/- 0.2 mg min-1 kg-1, days 2 and 7, respectively). Insulin-stimulated glucose uptake rate was halved on day two compared with sea level (4.5 +/- 0.6 and 9.8 +/- 1.1 mg min-1 kg-1, respectively; P < 0.05), and was partly restored on day 7 (7.4 +/- 1.4 mg min-1 kg-1; P < 0.05 vs. day two and sea level). Concentrations of glucagon and growth hormone remained unchanged, whereas glucose, C-peptide and cortisol increased on day 2. Noradrenaline concentrations increased during the stay at altitude, while adrenaline concentrations remained unchanged. In response to insulin infusion, catecholamines increased on day 2 (noradrenaline and adrenaline) and day 7 (adrenaline), but not at sea level. 4. In conclusion, insulin action decreases markedly in response to two days of altitude hypoxia, but improves with more prolonged exposure. HGP is always unchanged. The changes in insulin action may in part be explained by the changes in counter-regulatory hormones.

Acclimatization↗
PubMed1997

Desensitization of human adipose tissue to adrenaline stimulation studied by microdialysis.

1. Desensitization of fat cell lipolysis to catecholamine exposure has been studied extensively in vitro but only to a small extent in human adipose tissue in vivo. 2. We measured interstitial glycerol concentrations by microdialysis in subcutaneous, abdominal adipose tissue in healthy humans during intravenous adrenaline infusion for three 35 min periods with 30 min breaks in between. Local blood flow, interstitial adrenaline and arterial glycerol concentrations were also measured. Adrenaline was infused to result in either a high, a low and a high arterial concentration (5.8, 3.1 and 5.6 nM, respectively) or a low, a high and a low concentration (2.5, 4.6 and 2.6 nM, respectively) in order to examine both desensitization and the dose dependency of adipose tissue lipolysis to adrenaline. 3. Adipose tissue lipolysis was calculated and was found to vary directly with arterial adrenaline concentration. However, lipolytic responses to adrenaline decreased markedly during repeated stimulation at a given concentration. Further, arterial glycerol and free fatty acid concentrations varied directly with arterial adrenaline concentrations and showed reduced responses upon repeated exposure. 4. The increase in adipose tissue blood flow in response to adrenaline was also reduced by prior adrenaline exposure, but no consistent desensitization could be demonstrated for whole-body energy expenditure, blood pressure and heart rate. 5. In the basal state, arterial plasma and interstitial adrenaline concentrations did not differ. During perturbations of arterial adrenaline concentrations, changes in interstitial concentrations were highly reproducible but smaller than changes in arterial concentrations. 6. In conclusion, in vivo adrenaline-mediated adipose tissue lipolysis and blood flow increments are desensitized by prior adrenaline exposure.

3-Hydroxybutyric Acid↗
PubMed1997

Exercise-induced increase in serum interleukin-6 in humans is related to muscle damage.

1. This study was performed to test the hypothesis that the exercise-induced increase in circulating cytokine levels is associated with muscle damage. Nine healthy young male subjects performed two high-intensity bicycle exercise trials separated by two weeks. The first trial consisted of 30 min of normal bicycle exercise (concentric exercise), whereas the second consisted of 30 min of braking with reversed revolution (eccentric exercise). The work loads were chosen to give the same increases in heart rate and catecholamine levels in the blood during each trial. 2. Significant increases (P < 0.05) in plasma concentration of creatine kinase (CK), aspartate aminotransferase and alanine aminotransferase were observed only after the eccentric exercise. Furthermore, the level of interleukin-6 (IL-6) in serum increased significantly after the eccentric exercise and was significantly correlated to CK concentration in the following days, whereas no significant changes were found after the concentric exercise. 3. The total concentration of lymphocytes increased significantly (P < 0.05) as a result of eccentric compared with concentric exercise. This was mainly due to a significantly more pronounced recruitment of natural killer (NK) cells and CD8 positive cells (CD8+ cells) during the eccentric trial. However, no significant differences between the two types of work were found in regard to the circulating concentration of monocytes. The concentration of neutrophils was only significantly increased 2 h after the concentric exercise. 4. The finding that high-intensity eccentric exercise caused a more pronounced increase in the plasma level of IL-6, compared with concentric exercise, supports the hypothesis that the post-exercise cytokine production is related to skeletal muscle damage. The fact that no differences between eccentric and concentric exercise were found in the recruitment of most blood mononuclear cell subsets to the blood supports the hypothesis that the exercise-induced increase in plasma catecholamines is a major determinant of the mobilization of these cells into the blood. However, as eccentric exercise caused a more pronounced increase in the concentration of NK cells and CD8+ cells, factors involved in muscle damage may also contribute to the recruitment of these cells.

Adult↗
PubMed1997

The effect of moderate exercise on postprandial glucose homeostasis in NIDDM patients.

The influence of exercise on glycaemia in the post-prandial state was studied for the first time in non-insulin-dependent diabetic (NIDDM) patients. Meal-induced glucose responses were followed for 8 h in 9 diet-treated patients with NIDDM. Subjects consumed a standardized breakfast and 4 h later a standardized lunch. They were studied in the resting state (control day (CD)) and on another day 45 min of bicycle exercise (53 +/- 2% VO2max (mean +/- SEM)) was performed 45 min after breakfast (exercise day (ED)). On day 3 (diet day (DD)), the breakfast meal was reduced corresponding to the extra energy expenditure during the exercise period on ED. Responses were calculated as areas under the plasma concentration curve (AUC) during 4 h after either breakfast (B-AUC) or lunch (L-AUC). B-AUC for glucose was identical on ED (215 +/- 63 mmol/l.240 min) and DD (219 +/- 60 mmol/l.240 min) and on these days lower (p < 0.05) than on CD (453 +/- 78 mmol/l.240 min). L-AUC for glucose on CD, ED and DD did not differ significantly. B-AUCs for both insulin and C-peptide were also significantly lower on ED and DD as compared to CD (Insulin: 31337 +/- 8682, 26092 +/- 6457 and 47649 +/- 15046 mmol/l.240 min, respectively. C-peptide: 99 +/- 19, 104 +/- 26 and 195 +/- 31 pmol/ml.240 min, respectively). Rate of appearance (Ra) for glucose was unaffected by exercise whereas rate of disappearance (Rd) increased significantly. No differences in Ra or Rd were observed after lunch. In conclusion, post-prandial exercise of moderate intensity decreases glycaemia and plasma insulin levels after breakfast in NIDDM patients, but this effect does not persist during and after the following lunch meal. Reduction of breakfast caloric intake has the same effect on post-prandial glycaemia and insulin secretion as an equivalent exercise-induced increase in caloric expenditure.

Analysis of Variance↗
PubMed1997

Increased bone mineral density after prolonged electrically induced cycle training of paralyzed limbs in spinal cord injured man.

Spinal cord injured (SCI) individuals have a substantial loss of bone mass in the lower limbs, equaling approximately 50% of normal values in the proximal tibia, and this has been associated with a high incidence of low impact fractures. To evaluate if this inactivity-associated condition in the SCI population can be reversed with prolonged physical training, ten SCI individuals [ages 35.3 +/- 2.3 years (mean +/- standard error [SE]); post injury time: 12.5 +/- 2.7 years, range 2-24 years; level of lesion: C6-Th4; weight: 78 +/- 3.8 kg] performed 12 months of Functional Electrical Stimulated (FES) upright cycling for 30 min per day, 3 days per week, followed by six months with only one weekly training session. Bone mineral density (BMD) was determined before training and 12 and 18 months later. BMD was measured in the lumbar spine, the femoral neck, and the proximal tibia by dual energy absorptiometry (DEXA, Nordland XR 26 MK1). Before training, BMD was in the proximal tibia (52%), as well as in the femoral neck, lower in SCI subjects than in controls of same age (P < 0.05). BMD of the lumbar spine did not differ between groups (P > 0.05). After 12 months of training, the BMD of the proximal tibia had increased 10%, from 0.49 +/- 0.04 to 0. 54 +/- 0.04 g/cm2 (P < 0.05). After a further 6 months with reduced training, the BMD in the proximal tibia no longer differed from the BMD before training (P > 0.05). No changes were observed in the lumbar spine or in the femoral neck in response to FES cycle training. It is concluded that in SCI, the loss of bone mass in the proximal tibia can be partially reversed by regular long-term FES cycle exercise. However, one exercise session per week is insufficient to maintain this increase.

Absorptiometry, Photon↗
PubMed1997

Long-term adaptation to electrically induced cycle training in severe spinal cord injured individuals.

Spinal cord injured (SCI) individuals most often contract their injury at a young age and are deemed to a life of more or less physical inactivity. In addition to the primary implications of the SCI, severe SCI individuals are stigmatized by conditions related to their physically inactive lifestyle. It is unknown if these inactivity related conditions are potentially reversible and the aim of the present study was, therefore, to examine the effect of exercise on SCI individuals. Ten such individuals (six with tetraplegia and four with paraplegia; age 27-45 years; time since injury 3-23 years) were exercise trained for 1 year using an electrically induced computerized feedback controlled cycle ergometer. They trained for up to three times a week (mean 2.3 times), 30 min on each occasion. The gluteal, hamstring and quadriceps muscles were stimulated via electrodes placed on the skin over their motor points. During the first training bouts, a substantial variation in performance was seen between the subjects. A majority of them were capable of performing 30 min of exercise in the first bout; however, two individuals were only able to perform a few minutes of exercise. After training for 1 year all of the subjects were able to perform 30 min of continuous training and the work output had increased from 4 +/- 1 (mean +/- SE) to 17 +/- 2 Kilo Joules per training bout (P < 0.05). The maximal oxygen uptake during electrically induced exercise increased from 1.20 +/- 0.08 litres per minute measured after a few weeks habituation to the exercise to 1.43 +/- 0.09 litres per minute after training for 1 year (P < 0.05). Magnetic resonance cross sectional images of the thigh were performed to estimate muscle mass and an increase of 12% (mean, P < 0.05) was seen in response to 1 year of training. In biopsies taken before exercise various degrees of atrophy were observed in the individual muscle fibres, a phenomenon that was partially normalized in all subjects after training. The fibre type distribution in skeletal muscles is known to shift towards type IIB fibres (fast twitch, fast fatiguable, glycolytic fibres) within the first 2 years after the spinal cord injury. The muscle in the present investigation contained of 63% myosin heavy chain (MHC) isoform IIB, 33% MHC isoform IIA (fast twitch, fatigue resistant) and less than 5% MHC isoform I (slow twitch) before training. A shift towards more fatigue resistant contractile proteins was found after 1 year of training. The percentage of MHC isoform IIA increased to 61% of all contractile protein and a corresponding decrease to 32% was seen in the fast fatiguable MHC isoform IIB, whereas MHC isoform I only comprised 7% of the total amount of MHC. This shift was accompanied by a doubling of the enzymatic activity of citrate synthase, as an indicator of mitochondrial oxidative capacity. It is concluded that inactivity-associated changes in exercise performance capacity and skeletal muscle occurring in SCI individuals after injury are reversible, even up to over 20 years after the injury. It follows that electrically induced exercise training of the paralysed limbs is an effective rehabilitation tool that should be offered to SCI individuals in the future.

Adaptation, Physiological↗
PubMed1997

Effect of in vivo injection of cholera and pertussis toxin on glucose transport in rat skeletal muscle.

Cholera toxin (CTX) and pertussis toxin (PTX) were examined for their ability to inhibit glucose transport in perfused skeletal muscle. Twenty-five hours after an intravenous injection of CTX, basal transport was decreased approximately 30%, and insulin- and contraction-stimulated transport was reduced at least 86 and 49%, respectively, in both the soleus and red and white gastrocnemius muscles. In contrast, PTX treatment was much less efficient. Impairment of glucose transport appeared to develop 10-15 h after CTX administration, which coincided with development of hyperglycemia despite hyperinsulinimia, increased plasma free fatty acid levels, increased adenosine 3',5'-cyclic monophosphate (cAMP) concentrations in muscle, but no difference in plasma catecholamines. Twenty-five hours after CTX treatment, GLUT-4 protein in both soleus and red gastrocnemius muscles was decreased, whereas no change in GLUT-1 protein content was found. In contrast, GLUT-4 mRNA was unchanged, but transcripts for GLUT-1 were increased > or = 150% in all three muscles from CTX-treated rats. The findings suggest that CTX via increased cAMP impairs basal as well as insulin- and contraction-stimulated muscle glucose transport, at least in part from a decrease in intramuscular GLUT-4 protein.

Animals↗
PubMed1996

Exercise fuel mobilization in mitochondrial myopathy: a metabolic dilemma.

In mitochondrial myopathy, severely impaired muscle oxidative capacity poses a dilemma for metabolic regulation in exercise. We inquired whether fuel mobilization during exercise in mitochondrial myopathy is adjusted to the reduced capacity to oxidize substrate, or if fuel is mobilized in excess of oxidative capacity. Hormonal and metabolic responses to 20 minutes of cycle exercise were studied in 4 patients with mitochondrial myopathy working at near maximal effort and in 4 healthy matched controls. On 2 separate days, controls were studied at the same absolute (A) workload (9 +/- 3 W) and the same relative (R) workload (77 +/- 9 W) as performed by the patients. During exercise, average glucose production was higher in patients (28 +/- 5 micromol min(-1) kg(-1)) than in controls at both workloads (A, 12 +/- 1; R, 18 +/- 2 micromol min(-1) kg(-1)). Exercise-induced increases in plasma glucose, growth hormone, epinephrine, norepinephrine, corticotropin, and lactate, and decreases in plasma insulin and pH were also larger in patients compared with findings in controls at both workloads. In conclusion, mitochondrial myopathies are associated with excessive neuroendocrine responses and mobilization of glucose during exercise. These responses augment ATP synthesis but result in progressive accumulation of nonoxidized substrates. Apparently, substrate mobilization and neuroendocrine responses in exercise are linked to oxidative demand rather than to oxidative capacity in working muscle.

Adrenocorticotropic Hormone↗