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Biomedical subjects

H Galbo

Publications and source records attributed to H Galbo.

At least 19 recordsLinked to original sources

Kinetics of glucose transport in rat skeletal muscle membrane vesicles: effects of insulin and contractions.

To study the mechanism of acceleration of glucose transport in skeletal muscle after stimulation with insulin and contractions, we isolated a subcellular vesicular membrane fraction, highly enriched in the plasma membrane enzyme K(+)-stimulated p-nitrophenylphosphatase and also enriched in some intracellular membranes. Protein recovery, morphology, lipid content, marker enzyme activities, total intravesicular volume, Western blot quantitation of GLUT-1, and glucose-inhibitable cytochalasin B binding were identical in membrane fractions from control, insulin-stimulated, contraction-stimulated, and insulin- and contraction-stimulated muscle. Time course of D-[3H]glucose entry in membrane vesicles at equilibrium exchange conditions showed that initial rate of transport at 30 mM of glucose was increased 19-fold and that equilibrium distribution space was increased 4-fold in vesicles from maximum stimulated muscle. The effects of insulin and contractions on initial rate of transport as well as on equilibrium distribution space were additive, and stimulation increased the substrate saturability of glucose transport. Furthermore, cytochalasin B binding to membranes prepared by using less centrifugation time than usual showed that, after stimulation with insulin and contractions, at least 35% of the total number of glucose transporters were redistributed from one kind of vesicles to a more slowly sedimenting kind of vesicles, probably reflecting translocation within the membrane preparation from intracellular vesicles to the plasma membrane upon stimulation. In the present membrane preparation the effects of insulin and/or contractions on glucose transport resemble those seen in intact muscle, and the effects are thus not dependent on cellular integrity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Effect of training on insulin-mediated glucose uptake in human muscle.

During insulin stimulation whole body glucose uptake is increased in trained compared with untrained humans. However, it is not known which tissue is responsible. Seven young male subjects bicycle trained one leg for 10 wk at 70% of maximal O2 consumption (VO2max). Sixteen hours after last exercise bout, a three-step euglycemic hyperinsulinemic clamp (clamp 1) was performed (insulin levels, means +/- SE: 9 +/- 1, 53 +/- 3, 174 +/- 5, and 2,323 +/- 80 was microU/ml), with measurement of arteriovenous differences and blood flow in both legs. After 6 days of detraining subjects were restudied, having exercised the untrained leg 16 h before. VO2max for trained (T) and untrained (UT) legs was 52 +/- 2 vs. 44 +/- 2 ml.min-1.kg-1 (P < 0.05). In clamp 1 glucose uptake in T and UT legs was 1.0 +/- 0.2 vs. 0.5 +/- 0.1 mg.min-1.kg-1 (basal), 9.7 +/- 2.3 vs. 6.7 +/- 1.7 (P < 0.05) (step I), 19.2 +/- 2.8 vs. 14.3 +/- 2.0 (P < 0.05) (step II), and 22.8 +/- 2.3 vs. 18.6 +/- 2.2 (P < 0.05) (step III). During insulin infusion lactate release (P < 0.05) [8.9 +/- 1.8 vs. 2.9 +/- 0.9 mumol.min-1.kg-1 (step I), 24.6 +/- 3.1 vs. 12.5 +/- 2.6 (step III)] and glycogen storage (P < 0.1) calculated by indirect calorimetry [6.7 +/- 2.3 vs. 5.0 +/- 1.7 mg.min-1.kg-1 (step I), 16.8 +/- 2.1 vs. 14.1 +/- 1.8 (step III)] were always higher in T than in UT legs. Release of glycerol, free fatty acids, and tyrosine and clearance of insulin were not influenced by training. Insulin-mediated glucose uptake was not increased after detraining or a single bout of exercise. In conclusion, training increases sensitivity and responsiveness of insulin-mediated glucose uptake in human muscle by local mechanisms. Glycolysis and glycogen storage are equally enhanced. The training effect represents a genuine adaptation to repeated exercise but is short lived. Insulin clearance in muscle is not influenced by training.

Adult

Effect of 5 wk of detraining on epinephrine response to insulin-induced hypoglycemia in athletes.

Long-term endurance-trained subjects are known to have an enhanced capacity to secrete epinephrine. It is, however, unknown to what extent this is a reversible phenomenon, i.e., whether the adrenal medullary secretory capacity is diminished during a period of abstinence from training. Hormonal responses to insulin-induced hypoglycemia were studied in seven endurance-trained young male athletes at the onset and the termination of a 31- to 44-day period of detraining necessitated by a sports injury that required leg casting. During insulin infusion, plasma glucose decreased to a mean range of 2.0-2.1 mM for the two conditions. The epinephrine response to hypoglycemia did not decrease significantly during the 4-6 wk of detraining (P greater than 0.05). Responses of other counterregulatory hormones, i.e., norepinephrine, glucagon, growth hormone, and cortisol, were identical in trained and detrained subjects (P greater than 0.05). Heart rate and blood pressure responses to hypoglycemia were similar in the two conditions (P greater than 0.05). In conclusion, in endurance athletes the enhanced capacity to secrete epinephrine is maintained during 5 wk of detraining.

Adolescent

Effect of deficient muscular glycogenolysis on extramuscular fuel production in exercise.

Hormonal, metabolic, and cardiovascular responses to 21 min of cycling in three saline- or glucose-infused men with McArdle's disease were compared with those of matched controls to elucidate whether mobilization of extramuscular fuel is enhanced to compensate for the lack of intramuscular glycogenolysis in patients with McArdle's disease. During exercise, all saline-infused patients compared with controls working at both the same absolute and at similar relative work rates had higher glucose production (31 +/- 7 vs. 19 +/- 5 and 26 +/- 4 mumol.min-1.kg-1) and utilization (34 +/- 8 vs. 22 +/- 2 and 28 +/- 4 mumol.min-1.kg-1); higher plasma glycerol (155 +/- 19 vs. 75 +/- 20 and 90 +/- 22 mumol/l), free fatty acids (487 +/- 175 vs. 295 +/- 47 and 202 +/- 52 mumol/l), growth hormone (7.7 +/- 2.8 vs. 2.6 +/- 1.1 and 3.6 +/- 3.4 mU/l), and cortisol (530 +/- 168 vs. 268 +/- 8 and 367 +/- 80 nmol/l), greater decrease in insulin (delta 57 +/- 4 vs. delta 11 +/- 8 and delta 11 +/- 23 pmol/l), and similar glucose concentrations. Furthermore, norepinephrine, epinephrine, and adrenocorticotropic hormone levels were higher and heart rate and cardiac output were higher during exercise in all patients than in controls at the same absolute work rate. Glucose infusion induced hyperglycemia and hyperinsulinemia in patients and inhibited the exercise-induced increases in glucose production, glycerol, free fatty acids, catecholamines, growth hormone, cortisol, and heart rate. In conclusion, feedback from metabolism in contracting muscle enhances hormonal responses and extramuscular substrate mobilization during exercise in McArdle's disease.

Adult

Heart rate and plasma catecholamines during 24 h of everyday life in trained and untrained men.

Physical training decreases resting heart rate as well as heart rate and catecholamine responses to ordinary physical activity and mental stress. These effects have been speculated to diminish cardiac morbidity. However, the sparing of heartbeats and catecholamine production might be outweighed by exaggerated responses during training sessions. To elucidate this issue, heart rate was measured continuously and plasma catecholamine concentrations were measured frequently during 24 h of ordinary living conditions in seven endurance-trained athletes (T) and eight sedentary or untrained (UT) young males. T subjects had lower heart rates than UT subjects during sleep and during nontraining awake periods. However, because of the increase during training, the total 24-h heartbeat number did not differ between groups (107,737 +/- 3,819 for T vs. 113,249 +/- 6,879 for UT, P = 0.731). Neither during sleep nor during awake nontraining periods were catecholamine levels lower in T than in UT subjects. Peak catecholamine levels during exercise in T were much higher than peak levels in UT subjects, and 24-h average epinephrine and norepinephrine concentrations were twice as high. We concluded that in highly trained athletes the total number of heartbeats per day is not decreased and the catecholamine production is, in fact, increased.

Adult

Does training spare insulin secretion and diminish glucose levels in real life?

Compared with untrained subjects, in trained subjects the increased insulin sensitivity and decreased glucose induced insulin secretion will tend to promote health by decreasing glucose levels and insulin secretion, whereas the increased food intake will tend to increase these variables. To evaluate the net effect of training, we administered oral glucose loads making up identical fractions of daily carbohydrate intake (i.e., same relative glucose loads) to 8 athletes and 7 sedentary subjects (age: 25 +/- 1 vs. 24 +/- 1 yr [mean +/- SE] [NS]; body weight: 76.0 +/- 1.3 vs. 79.3 +/- 2.3 kg [NS]; maximal oxygen uptake: 76 +/- 2 vs. 48 +/- 1 ml O2.kg-1.min-1 [2P < 0.05], respectively). Furthermore, 24 h plasma concentration profiles of glucose, C-peptide, and insulin were determined during ordinary living conditions. Daily carbohydrate intake was higher (2P < 0.05) in athletes compared with sedentary subjects (678 +/- 34 vs. 294 +/- 18 g.day-1, respectively). In response to same relative oral glucose loads, glucose and C-peptide responses were similar in athletes compared to sedentary subjects. Twenty-four hour integrated glucose and C-peptide concentrations did not differ between athletes and sedentary subjects (7.4 +/- 0.2 vs. 7.3 +/- 0.6 mol.L-1.1440 min [2P > 0.05] and 923 +/- 99 vs. 1047 +/- 175 pM.ml-1.1440 min [2P > 0.05], respectively), and insulin concentrations tended to be lower in athletes compared with sedentary subjects (124 +/- 13 vs. 175 +/- 38 pM.ml-1.1440 min [2P > 0.05]).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Increased activities of mitochondrial enzymes in white adipose tissue in trained rats.

During earlier fat cell studies we noticed that homogenates of white fat cells became more brown with training, a fact that might reflect an increased content of mitochondria. This raised the question whether training (as is the case in muscle) increases the oxidative capacity in fat cells. Groups of 8-12 rats were swim trained for 10 wk or served as either sedentary, sham swim-trained, or cold-stressed controls. White adipose tissue was removed, and the activities of the respiratory chain enzyme cytochrome-c oxidase (CCO) and of the enzyme malate dehydrogenase (MDH), which participates in the tricarboxylic acid cycle as well as in the mitochondrial malate-aspartate and acetyl-group shuttles, were determined. The CCO and MDH activities expressed per milligram protein were increased in male rats 4.4- and 2.8-fold, respectively, in the swim-trained compared with the sham swim-trained rats (P less than 0.05). In female rats the CCO activity expressed per milligram protein was increased 4.5-fold in the trained compared with the sedentary control rats (P less than 0.01). Neither cold stress nor sham swim training increased CCO or MDH activities in white adipose tissue (P greater than 0.05). In conclusion, in rats, intensive endurance training induces an increase in mitochondrial enzyme activities in white adipose tissue as is seen in skeletal muscle.

Adipose Tissue

The effect of water temperature on the hormonal response to prolonged swimming.

The relationship between thermoreception, hormonal secretion and muscular activity was studied. 6 men swam 60 min in 21, 27 and 33 degrees C water at a speed requiring 68% of VO2 max (determined in 27 degrees C water). Rectal temperature increased in 33 degrees C (1.3 +/- 0.2 degrees C, mean and S.E.) and 27 degrees C (0.7+/- 0.1 degrees C) expts. but decreased in 21 degrees C expts. (0.8 +/- 0.3 degrees C). Changes in esophageal and muscle temperatures parallelled changes in rectal temperature. Plasma noradrenaline was higher in 33 degrees C than in 27 degrees C expts. and growth hormone, cortisol and glucagon concentrations increased in 27 degrees C and 33 degrees C expts. only. Insulin concentrations were uniformly depressed during swimming at the different water temperatures. In 21 degrees C expts. noradrenaline and adrenaline concentrations were higher than in 27 degrees C expts. VO2, carbohydrate combustion and peak lactate were slightly lower in 33 degrees C expts. Plasma glucose decreased slightly and FFA and glycerol concentrations increased identically in all expts. Heart rate increased continuously during swimming in 27 degrees C and 33 degrees C expts., but not in 21 degrees C expts. In conclusion the rise in body temperatures normally observed during exercise enhances the exercise induced increases in the plasma concentrations of noradrenaline, cortisol, growth hormone and glucagon. Decreased body temperatures may elicit catecholamine secretion as a direct consequence of thermoreception. Shivering may account for previously observed decreases in insulin secretion during cold stress but not for increases in cortisol and growth hormone.

Adult

Fasting and prolonged exercise increase vasoactive intestinal polypeptide (VIP) in plasma.

6 young men had venous blood drawn during 4 experiments. The concentration of VIP in plasma increased markedly (from 1.8 (0--4.5) to 22.3 (7.8--43.8) pmol.1(-1), mean and range) during 3 h of mild bicycle exercise but not at all during an equivalent period of rest or during short term submaximal and maximal exercise. During 59 h of fasting, VIP increased from 3.6 (0.6--6.6) to 10.2 (6.6--13.8) pmol.1(-1) (p less than 0.05). The concentration of glucose in plasma decreased significantly during the prolonged exercise as well as during fasting. The known metabolic actions of VIP and the demonstrated increases in its plasma concentration during negative energy balance indicate that VIP is "a polypeptide of substrate need".

Adolescent

The effect of different diets and of insulin on the hormonal response to prolonged exercise.

UNLABELLED: The importance of carbohydrate availability during exercise for metabolism and plasma hormone levels was studied. Seven healthy men ran on a treadmill at 70% of individual maximal oxygen uptake having eaten a diet low (F) or high (CH) in carbohydrate through 4 days. At exhaustion the subjects were encouraged to continue to run while glucose infusion increased plasma glucose to preexercise levels. Forearm venous blood, biopsies from vastus muscle and expiratory gas were analyzed. Time to exhaustion was longer in CH- (106 +/- 5 min (S.E.)) than in F-expts. (64 +/- 6). During exercise, overall carbohydrate combustion rate, muscular glycogen depletion and glucose and lactate concentrations, carbohydrate metabolites in plasma, and estimated rate of hepatic glucose production were higher, fat metabolites lower, and the decrease in plasma glucose slower in CH- than in F-expts. Plasma norepinephrine increased and insulin decreased similarly in CH- and F-expts., whereas the increase in glucagon, epinephrine, growth hormone and cortisol was enhanced in F-expts. Glucose infusion eliminated hypoglycemic symptoms but did not substantially increase performance time. During the infusion epinephrine decreased markedly and glucagon even to preexercise levels. Infusion of insulin (to 436% of preexercise concentration) in addition to glucose in F-expts. did not change the plasma levels of the other hormones more than infusion of glucose only but reduced fat metabolites in plasma. At exhaustion muscular glycogen depletion was slow, and the glucose gradient between plasma and sarcoplasma as well as the muscular glucose 6-phosphate concentration had decreased. CONCLUSIONS: The preceding diet modifies the energy depots, the state of which (as regards size, receptors and enzymes) is of prime importance for metabolism during prolonged exercise. Plentiful carbohydrate stores favor both glucose oxidation and lactate production. During exercise norepinephrine increases and insulin decreases independent of plasma glucose changes whereas receptors sensitive to glucose privation but not to acute changes in insulin levels enhance the exercise-induced secretion of glucagon, epinephrine, growth hormone and cortisol. Abolition of cerebral hypoglycemia does not inevitably increase performance time, because elimination of the hypoglycemia may not abolish muscular energy lack.

Adult

Increased hepatic glycogen synthetase and decreased phosphorylase in trained rats.

Rats were either physically trained by a 12 wk swimming program or were freely eating or weight matched, sedentary controls. Trained rats had a higher relative liver weight and total hepatic glycogen synthetase (EC 2.4.1.11) activity and a lower phosphorylase (EC 2.4.1.1) activity than the other groups of rats. These changes may partly explain the demonstrated training-induced increase in glucose tolerance. None of the findings could be ascribed to differences in foold intake or body weight.

Animals

Sympathetic control of metabolic and hormonal responses to exercise in rats.

The importance of the sympatho-adrenal system for the pancreatic hormonal response to exercise and, furthermore, the role of glucagon and catecholamines for the hepatic glycogen depletion during exercise were studied. Rats were either surgically adrenomedullectomized and chemically sympathectomized with 6-hydroxydopamine or shamtreated. Two weeks later the rats had either rabbit-antiglucagon serum or normal rabbit serum injected. Subsequently the rats either rested or swam with a tail weight for 75 min. Immediately afterwards cardiac blood was drawn and liver and muscle tissue collected. In control rats in spite of an increase in blood glucose concentrati4ns during exercise plasma insulin concentrations were unchanged, while glucagon concentrations increased. In sympathectomized rats, compared to control rats, glucagon concentrations increased less, and insulin concentrations were higher, although glucose concentrations were lower during exercise. Sympathectomy completely abolished the exercise-induced decrease in liver and muscle glycogen concentrations, whereas neither glycogen depletion nor plasma catecholamine concentrations were influenced by the administration of glucagon antibodies. These findings indicate that the sympatho-adrenal system enhances glucagon secretion as well as muscular and hepatic glycogen depletion but inhibits insulin secretion in exercising rats. The increase in glucagon concentrations, however, does not enhance hepatic glycogen depletion at the work load used.

Adrenal Medulla

Influence of the autonomic nervous system on the release of vasoactive intestinal polypeptide from the porcine gastrointestinal tract.

1. The release of vasoactive intestinal polypeptide from the gastrointestinal tract in response to stimulation of the vagus nerves, the splanchnic nerves and to intra-arterial infusion of acetylcholine (ACh) was examined in pigs. 2. Stimulation of the vagus nerves caused an abrupt increase in the release of vasoactive intestinal polypeptide. The amount of the peptide released depended on the frequency at which the nerves were stimulated. Maximum release was obtained at 8 Hz. 3. Atropine and beta-adrenergic blocking agents failed to diminish the vagally induced release of vasoactive intestinal polypeptide, while the response was completely blocked by hexamethonium and increased after alpha-adrenergic blockade and after splanchnicotomy. 4. Intra-arterial infusion of ACh closely imitated the response to vagal stimulation, but the release of vasoactive intestinal polypeptide induced by ACh was abolished by atropine. 5. Stimulation of the splanchnic nerves caused a decrease in the release of vasoactive intestinal polypeptide, an action which was annulled by alpha-adrenergic blockade, but still present after the adrenal glands were isolated from the circulation. The inhibitory effect of splanchnic stimulation significantly diminished the vagally induced release of vasoactive intestinal polypeptide. 6. The results demonstrate a dual innervation with opposing effects on the neurones containing vasoactive intestinal polypeptides. The possible physiologic implication of this finding is discussed.

Acetylcholine

Neutralization of glucagon by antiserum as a tool in glucagon physiology. Lack of depression of basal blood glucose after antiserum treatment in rats.

The method of producing experimental glucagon deficiency by administration of glucagon antiserum was evaluated in rats. A pool of antisera was prepared, the affinity of which exceeded that of the glucagon receptors of liver cell membranes, whereas the binding capacity of the volume used amounted to more than one-third of the total glucagon content in the rat pancreas. That rapid, extensive, and lasting neutralization of glucagon had taken place after antiserum treatment was indicated by the following findings: When examined more than 1 h after the injection and after 60 min of exercise-stimulated glucagon production, all rats had excess free antibodies in plasma. The concentration of free glucagon was lowered to one-third of the concentration in control rats; at 37 degrees C plasma samples could bind 25% of additional 300 pmol/liter of glucagon in 10 s, and 69% in 120 s; the glycemic response to exogenous glucagon was abolished. Antiserum treatment, however, had no effect on blood glucose in rats fasted for 3 and 10 h, in chemically sympathectomized and adrenomedullectomized rats, and in 48-h-fasted, acutely adrenalectomized rats. The antiserum was found to contain 460 nmol/liter of antibody-bound glucagon, originating in the rabbit in which the antiserum was raised. However, antibody preparations from which the bound glucagon had been effectively removed were equally ineffective in lowering the basal blood glucose in rats, although in three-fourths of the rats the concentration of free glucagon was lowered beyond detection limit. The data indicate that the absolute concentration of glucagon in plasma is of minor importance for the maintenance of basal blood glucose in the rat.

Animals