IGF-1 response to arm exercise with eccentric and concentric muscle contractions in resistance-trained athletes with left ventricular hypertrophy.

The study aimed at evaluating changes in plasma levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3), testosterone, growth hormone (GH), cortisol, and insulin in resistance-trained male athletes with (n=9) and without (n=9) left ventricular hypertrophy (LVH) in response to eccentric (ECC) and concentric (CON) arm exercise. 10 age-matched healthy non-trained subjects served as controls. M-mode and 2D Doppler echocardiography were used to estimate LV mass.Resting IGF-1 concentration was higher in LVH athletes compared to controls (52 ± 5 nM vs. 46 ± 7 nM, p<0.05). ECC exercise resulted in higher (p<0.05) serum IGF-1 concentrations in athletes with LVH (70 ± 11 nM, n=9) compared to those without LVH (62 ± 10 nM, n=9), and to untrained controls (54 ± 6 nM). Both CON and ECC exercise resulted in higher serum IGFBP-3 levels in LVH athletes compared to controls (242 ± 57 and 274 ± 58, athletes, vs. 215 ± 63 and 244 ± 67, controls, nM, p<0.05). In ECC exercise, GH concentrations were lower in LVH than in non-LVH athletes (4.7 ± 2.1 vs. 6.1 ± 1.8 ng mL(-1), p<0.05). No differences in other hormones were found between groups. In conclusion, LVH is accompanied by elevated resting serum IGF-1 and enhanced response to eccentric arm exercise. These findings suggest a role of IGF-1, possibly released from contracting muscle, in stimulating LV hypertrophy in resistance training.

Muscle ceramide content is similar after 3 weeks' consumption of fat or carbohydrate diet in a crossover design in patients with type 2 diabetes.

This study aimed at investigating the effect of prolonged adaptation to fat- or carbohydrate-rich diet on muscle ceramide in type 2 diabetes patients, using a longitudinal crossover study. Eleven type 2 diabetes patients consumed isocaloric fat- or carbohydrate-rich diet for 3 weeks in random order. After each dietary intervention period, muscle glycogen, triacylglycerol and ceramide content and plasma concentrations of insulin, adiponectin, glucose and FFA were determined. Insulin resistance was assessed by HOMA2 calculation. After the dietary period, plasma glucose and insulin, insulin sensitivity, muscle glycogen, triacylglycerol and ceramide content were similar. Plasma adiponectin concentration was significantly higher after fat compared with carbohydrate-rich diet. Results indicated that following fat-rich diet intake muscle ceramide and triacylglycerol concentrations were not different compared with that after carbohydrate-rich diet. Furthermore, plasma adiponectin concentration was higher after fat-rich compared with carbohydrate-rich diet, but insulin sensitivity remained similar despite the major difference in dietary macronutrient composition.

Vascular and metabolic effects of adrenaline in adipose tissue in type 2 diabetes.

OBJECTIVE: The aim was to investigate adipose tissue vascular and metabolic effects of an adrenaline infusion in vivo in subjects with and without type 2 diabetes mellitus (T2DM). DESIGN: Clinical intervention study with 1-h intravenous adrenaline infusion. SUBJECTS: Eight male overweight T2DM subjects and eight male weight-matched, non-T2DM subjects were studied before, during and after an 1-h intravenous adrenaline infusion. Adipose tissue blood flow (ATBF) was determined by (133)Xenon wash-out technique, and microvascular volume in the adipose tissue was studied by contrast-enhanced ultrasound imaging. Adipose tissue fluxes of glycerol, non-esterified fatty acids (NEFA), triacylglycerol and glucose were measured by Fick's principle after catherisation of a radial artery and a vein draining the abdominal, subcutaneous adipose tissue. RESULTS: ATBF increased similarly in both groups during the adrenaline infusion. One hour post adrenaline, ATBF was still increased in overweight T2DM subjects. Adrenaline increased microvascular volume in non-T2DM subjects while this response was impaired in overweight T2DM subjects. Adrenaline-induced increase in lipolysis was similar in both groups, but NEFA output from adipose tissue was delayed in overweight T2DM subjects. Glucose uptake in adipose tissue increased in non-T2DM subjects during adrenaline infusion but was unchanged in overweight T2DM subjects. This results in a delayed excess release of NEFA from the adipose tissue in overweight T2DM subjects after cessation of the adrenaline infusion. CONCLUSION: Capillaries in the adipose tissue are recruited by adrenaline in non-T2DM subjects; however, this response is impaired in overweight T2DM subjects. NEFA, released in adipose tissue during adrenaline stimulation, is insufficiently re-esterified in situ in overweight T2DM subjects, probably owing to increased ATBF after adrenaline infusion and inability to increase adipose tissue glucose uptake.

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans.

AIM/HYPOTHESIS: The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserved in leg and arm muscles after weight loss. METHODS: Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsy samples were obtained from musculus deltoideus (m. deltoideus) and m. vastus lateralis muscles. Fibre-type composition, enzyme activity and O(2) flux capacity of saponin-permeabilized muscle fibres were measured, the latter by high-resolution respirometry. RESULTS: During the graded exercise tests, peak fat oxidation during leg cycling and the relative workload at which it occurred (FatMax) were higher in PO and O than in C. During arm cranking, peak fat oxidation was higher in O than in C, and FatMax was higher in O than in PO and C. Similar fibre-type composition was found between groups. Plasma adiponectin was higher in PO than in C and O, and plasma leptin was higher in O than in PO and C. CONCLUSIONS: In O subjects, maximal fat oxidation during exercise and the eliciting relative exercise intensity are increased. This is associated with higher intramuscular triglyceride levels and higher resting non esterified fatty acid (NEFA) concentrations, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.

Insulin sensitivity and related cytokines, chemokines, and adipokines in polymyalgia rheumatica.

OBJECTIVES: To evaluate the insulin sensitivity (IS) and levels of peptides with impact on IS in polymyalgia rheumatica (PMR) before and after prednisolone treatment. METHODS: Fifteen PMR patients and 15 controls were included. Subjects were studied before and after treatment with prednisolone for 14 days (20 mg/day). Composite IS indices were calculated from glucose and insulin concentrations during an oral glucose tolerance test (OGTT). Plasma concentrations of tumour necrosis factor alpha (TNF), interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1 (MCP-1), resistin, leptin, and adiponectin were measured. RESULTS: Prednisolone abolished symptoms and increased physical activity within 1–2 days; erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were normalized at day 14. Before treatment, IS was lower in patients vs. controls (p < 0.001). Following treatment, IS was restored in patients (p < 0.01) but not changed in controls (p > 0.05). IL-6, TNF, and IL-8 were higher in patients vs. controls before treatment (p < 0.05–0.001), and decreased after treatment in patients (p < 0.001) but did not change in controls. Before treatment, adiponectin was lower in patients vs. controls (p < 0.05). During treatment, adiponectin increased in both groups (p < 0.05). Leptin did not differ between untreated patients and controls but increased in both groups (p < 0.05). MCP-1 and resistin did not differ (p > 0.05). CONCLUSION: IS is decreased in PMR, probably reflecting abnormal cytokine and adipokine levels. Treatment with prednisolone improves IS along with normalization of cytokine and adipokine levels and physical activity.

The effect of exercise on postprandial lipidemia in type 2 diabetic patients.

To elucidate if postprandial exercise can reduce the exaggerated lipidemia seen in type 2 diabetic patients after a high-fat meal. Two mornings eight type 2 diabetic patients (males) (58 +/- 1.2 years, BMI 28.0 +/- 0.9 kg m(-2)) and seven non-diabetic controls ate a high-fat breakfast (680 kcal m(-2), 84% fat). On one morning, 90 min later subjects cycled 60 min at 57% VO(2max). Biopsies from quadriceps muscle and abdominal subcutaneous adipose tissue were sampled after exercise or equivalent period of rest and arterialized blood for 615 min. Postprandial increases in serum total-triglyceride (TG) (incremental AUC: 1,702 +/- 576 vs. 341 +/- 117 mmol l(-1) 600 min), chylomicron-TG (incremental AUC: 1,331 +/- 495 vs. 184 +/- 55 mmol l(-1) 600 min) and VLDL-TG as well as in insulin (incremental AUC: 33,946 +/- 7,414 vs. 13,670 +/- 3,250 pmol l(-1) 600 min), C-peptide and glucose were higher in diabetic patients than in non-diabetic controls (P < 0.05). In diabetic patients these variables were reduced (P < 0.05) by exercise (total-TG incremental AUC being 1,110 +/- 444, chylomicron-TG incremental AUC 1,043 +/- 474 mmol l(-1) 600 min and insulin incremental AUC 18,668 +/- 4,412 pmol l(-1) 600 min). Lipoprotein lipase activity in muscle (11.0 +/- 2.0 vs. 24.1 +/- 3.4 mU g per wet weight, P < 0.05) and post-heparin plasma at 615 min were lower in diabetic patients than in non-diabetic controls, but did not differ in adipose tissue and did not change with exercise. In diabetic patients, 210 min after exercise oxygen uptake (P < 0.05) and fat oxidation (P < 0.1) were still higher than on non-exercise days. In type 2 diabetic patients, after a high-fat meal exercise reduces the plasma concentrations of triglyceride contained in both chylomicrons and VLDL as well as insulin secretion. This suggests protection against progression of atherosclerosis and diabetes.

Interstitial glycerol concentrations in human skeletal muscle and adipose tissue during graded exercise.

AIM: It is not clear how lipolysis changes in skeletal muscle and adipose tissue during exercise of different intensities. We aimed at estimating this by microdialysis and muscle biopsy techniques. METHODS: Nine healthy, young men were kicking with both legs at 25% of maximal power (Wmax) for 45 min and then simultaneously with one leg at 65% and the other leg at 85% Wmax for 35 min. RESULTS: Glycerol concentrations in skeletal muscle and adipose tissue interstitial fluid and in arterial plasma increased (P<0.001) during low intensity exercise and increased (P<0.05) even more during moderate intensity exercise. The difference between interstitial muscle and arterial plasma water glycerol concentration, which indicates the direction of the glycerol flux, was positive (P<0.05) at rest (21 +/- 9 microM) and during exercise at 25% Wmax (18 +/- 6 microM). The difference decreased (P<0.05) with increasing exercise intensity and was not significantly different from zero during exercise at 65% (-11 +/- 17 microM) and 85% (-12 +/- 13 microM) Wmax. In adipose tissue, the difference between interstitial and arterial plasma water glycerol increased (P<0.001) with increasing intensity. The net triacylglycerol breakdown, measured chemically from the biopsy, did not differ significantly from zero at any exercise intensity although directional changes were similar to microdialysis changes. CONCLUSIONS: Skeletal muscle releases glycerol at rest and at low exercise intensity but not at higher intensities. This can be interpreted as skeletal muscle lipolysis peaking at low exercise intensities but could also indicate that glycerol is taken up in skeletal muscle at a rate which is increasing with exercise intensity.

Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms.

AIM: The enzymatic regulation of intramuscular triacylglycerol (TG) breakdown has until recently not been well understood. Our aim was to elucidate the role of hormone-sensitive lipase (HSL), which controls TG breakdown in adipose tissue. METHODS: Isolated rat muscle as well as exercising humans were studied. RESULTS: The presence of HSL was demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative than in glycolytic fibres. Analysed under conditions optimal for HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via beta-adrenergic activation of protein kinase A (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser563, Ser659 and Ser660. Contraction probably also enhances muscle-HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is increased by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser600. So, phosphorylation of different sites may explain that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases the contraction-mediated, but diminishes the adrenaline mediated HSL activation in muscle. CONCLUSION: The existence and regulation of HSL in skeletal muscle indicate a role of HSL in muscle TG metabolism.

Additivity of adrenaline and contractions on hormone-sensitive lipase, but not on glycogen phosphorylase, in rat muscle.

AIM: Hormone-sensitive lipase (HSL) has been proposed to regulate triacylglycerol (TG) breakdown in skeletal muscle. In muscles with different fibre type compositions the influence on HSL of two major stimuli causing TG mobilization was studied. METHODS: Incubated soleus and extensor digitorum longus (EDL) muscles from 70 g rats were stimulated by adrenaline (5.5 microm, 6 min) or contractions (200 ms tetani, 1 Hz, 1 min) in maximally effective doses or by both adrenaline and contractions. RESULTS: Hormone-sensitive lipase activity was increased significantly by adrenaline as well as contractions, and the highest activity (P < 0.05) was seen with combined stimulation [Soleus: 0.40 +/- 0.03 (SE) m-unit mg protein(-1) (basal), 0.65 +/- 0.02 (adrenaline), 0.65 +/- 0.03 (contractions), 0.78 +/- 0.03 (adrenaline and contractions); EDL: 0.18 +/- 0.01, 0.30 +/- 0.02, 0.26 +/- 0.02, 0.32 +/- 0.01]. Glycogen phosphorylase activity was always increased more by adrenaline compared with contractions [Soleus: 60 +/- 4 (a/a + b)% vs. 46 +/- 3 (P < 0.05); EDL: 60 +/- 5 vs. 39 +/- 6 (P < 0.05)]. After combined stimulation glycogen phosphorylase activity in soleus [59 +/- 3 (a/a + b)%] was identical to and in EDL [45 +/- 4 (a/a + b)%] smaller (P < 0.05) than the activity after adrenaline only. CONCLUSIONS: In slow-twitch oxidative as well as in fast-twitch glycolytic muscle HSL is activated by both adrenaline and contractions. These stimuli are partially additive indicating at least partly different mechanisms of action. Contractions may impair the enhancing effect of adrenaline on glycogen phosphorylase activity in muscle.

Tender points are not sites of ongoing inflammation -in vivo evidence in patients with chronic tension-type headache.

Increased muscle tenderness is the most prominent finding in patients with tension-type headache, and it has recently been shown that muscle blood flow is diminished in response to static exercise in tender points in these patients. Although tenderness has been ascribed to local inflammation and release of inflammatory mediators, the interstitial concentration of inflammatory mediators has not previously been studied in tender muscles of patients with tension-type headache. The aim of the present study was to investigate in vivo concentrations of prostaglandin E2 (PGE2), adenosine 5'-triphosphate (ATP), glutamate, bradykinin and other metabolites in a tender point of patients with chronic tension-type headache, in the resting state as well as in response to static exercise, and to compare findings with measurements in a matched non-tender point of healthy controls. We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle and dialysates were collected at rest, 15 and 30 min after start of static exercise (10% of maximal force) and 15 and 30 min after end of exercise. All samples were coded and analysed blindly. There was no difference in resting concentration of any inflammatory mediators or metabolites between tender patients and non-tender controls (P > 0.05). We also found no difference in change in interstitial concentration of ATP, PGE2, glutamate, glucose, pyruvate and urea from baseline to exercise and post-exercise periods between patients and controls (P > 0.05). The present study provides in vivo evidence of normal interstitial levels of inflammatory mediators and metabolites in tender trapezius muscle in patients with chronic tension-type headache during both rest and static exercise. Thus, our data suggest that tender points in these patients are not sites of ongoing inflammation.

In vivo evidence of altered skeletal muscle blood flow in chronic tension-type headache.

Painful impulses from tender pericranial muscles may play a major role in the pathophysiology of chronic tension-type headache. Firm evidence for peripheral muscle pathology as a cause of muscle pain and chronic headache is still lacking. Using a microdialysis technique, we aimed to estimate in vivo blood flow and interstitial lactate concentrations in the trapezius muscle at rest and during static exercise in patients with chronic tension-type headache and in healthy subjects. We recruited 16 patients with chronic tension-type headache and 17 healthy control subjects. Two microdialysis catheters were inserted into the trapezius muscle (on the non-dominant side) of subjects, and dialysates were collected at rest, 15 and 30 min after the start of static exercise (10% of maximal force) and 15 and 30 min after the exercise was completed. All samples were coded and analysed blind. The primary endpoints were to detect a difference between patients and controls in changes of muscle blood flow and the interstitial lactate concentration from baseline to exercise and post-exercise periods. The increase in muscle blood flow from baseline to exercise and post-exercise periods was significantly lower in patients than controls (P = 0.03). There was no difference in resting blood flow between patients and controls (P = 0.43). Resting interstitial concentration of lactate did not differ between patients (2.51 +/- 0.18 mM; mean +/- standard error of the mean) and controls (2.35 +/- 0.23 mM, P = 0.57). There was no difference in change in interstitial lactate from baseline to exercise and post-exercise periods between patients and controls (P = 0.38). The present study provides in vivo evidence of decreased blood flow in response to static exercise in a tender muscle in patients with chronic tension-type headache. We suggest that, because of increased excitability of neurones in the CNS, the central interpretation and response to normal sensory input are altered in patients with chronic tension-type headache. This may lead to enhanced sympathetically mediated vasoconstriction and thereby a decreased blood flow in response to static exercise.

The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle.

1. Adrenaline-stimulated lipolysis in adipose tissue may increase with training. The rate-limiting step in adipose tissue lipolysis is catalysed by the enzyme hormone-sensitive lipase (HSL). We studied the effect of exercise training on the activity of the total and the activated form of HSL, referred to as HSL (DG) and HSL (TG), respectively, and on the concentration of HSL protein in retroperitoneal (RE) and mesenteric (ME) adipose tissue, and in the extensor digitorum longus (EDL) and soleus muscles in rats. 2. Rats (weighing 96 +/- 1 g, mean +/- S.E.M.) were either swim trained (T, 18 weeks, n = 12) or sedentary (S, n = 12). Then RE and ME adipose tissue and the EDL and soleus muscles were incubated for 20 min with 4.4 microM adrenaline. 3. HSL enzyme activities in adipose tissue were higher in T compared with S rats. Furthermore, in RE adipose tissue, training also doubled HSL protein concentration (P < 0.05). In ME adipose tissue, the HSL protein levels did not differ significantly between T and S rats. In muscle, HSL (TG) activity as well as HSL (TG)/HSL (DG) were lower in T rats, whereas HSL (DG) activity did not differ between groups. Furthermore, HSL protein concentration in muscle did not differ between T and S rats (P > 0.05). 4. In conclusion, training increased the amount of HSL and the sensitivity of HSL to stimulation by adrenaline in intra-abdominal adipose tissue, the extent of the change differing between anatomical locations. In contrast, in skeletal muscle the amount of HSL was unchanged and its sensitivity to stimulation by adrenaline reduced after training.

Splanchnic blood flow and hepatic glucose production in exercising humans: role of renin-angiotensin system.

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O(2) consumption (VO(2 max)) followed by 30 min at 70% VO(2 max) either with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an approximately 20-fold increase (P < 0.001) in ANG II levels in the control group (5.4 +/- 1.0 to 102.0 +/- 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 +/- 1.2 to 13.2 +/- 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, VO(2), and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 +/- 0.12, ACE blockade; 1.59 +/- 0.18 l/min, control) decreased during moderate exercise (0.78 +/- 0.07, ACE blockade; 0.74 +/- 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 +/- 0.06, ACE blockade; 0.68 +/- 0.10 mmol/min, control) increased during moderate exercise (1.97 +/- 0.29, ACE blockade; 1.91 +/- 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.

Role of the sympathoadrenergic system in adipose tissue metabolism during exercise in humans.

1. The relative roles of sympathetic nerve activity and circulating catecholamines for adipose tissue lipolysis during exercise are not known. 2. Seven paraplegic spinal cord injured (SCI, injury level T3-T5) and seven healthy control subjects were studied by microdialysis and (133)xenon washout in clavicular (Cl) and in umbilical (Um) (sympathetically decentralized in SCI) subcutaneous adipose tissue during 1 h of arm cycling exercise at approximately 60 % of the peak rate of oxygen uptake. 3. During exercise, adipose tissue blood flow (ATBF) and interstitial glycerol, lactate and noradrenaline concentrations increased significantly in both groups. Plasma catecholamine levels increased significantly less with exercise in SCI than in healthy subjects. The exercise-induced increase in interstitial glycerol concentration in subcutaneous adipose tissue was significantly lower in SCI compared with healthy subjects (SCI: 25 +/- 12 % (Cl), 36 +/- 20 % (Um); healthy: 60 +/- 17 % (Cl), 147 +/- 45 % (Um)) and the increase in ATBF was significantly lower (Cl) or similar (Um) in SCI compared with healthy subjects (SCI: 1.2 +/- 0.3 ml (100 g)(-1) min(-1) (Cl), 1.0 +/- 0.3 ml (100 g)(-1) min(-1) (Um); healthy: 2.8 +/- 0.7 ml (100 g)(-1) min(-1) (Cl), 0.6 +/- 0.3 ml (100 g)(-1) min(-1) (Um)). Accordingly, in both adipose tissues lipolysis increased less in SCI compared with healthy subjects, indicating that circulating catecholamines are important for the exercise-induced increase in subcutaneous adipose tissue lipolysis. In SCI subjects, the exercise-induced increase in subcutaneous adipose tissue lipolysis was not lower in decentralized than in sympathetically innervated adipose tissue. During exercise the interstitial noradrenaline and adrenaline concentrations were lower in SCI compared with healthy subjects (P < 0.05) and always lower than arterial plasma catecholamine concentrations (P < 0.05). 4. It is concluded that circulating catecholamines are important for the exercise-induced increase in subcutaneous adipose tissue lipolysis while sympathetic nerve activity is not.

Fatty acid kinetics and carbohydrate metabolism during electrical exercise in spinal cord-injured humans.

Motor center activity and reflexes from contracting muscle have been shown to be important for mobilization of free fatty acids (FFA) during exercise. We studied FFA metabolism in the absence of these mechanisms: during involuntary, electrically induced leg cycling in individuals with complete spinal cord injury (SCI). Healthy subjects performing voluntary cycling served as controls (C). Ten SCI (level of injury: C5-T7) and six C exercised for 30 min at comparable oxygen uptake rates (approximately 1 l/min), and [1-14C]palmitate was infused continuously to estimate FFA turnover. From femoral arteriovenous differences, blood flow, muscle biopsies, and indirect calorimetry, leg substrate balances as well as concentrations of intramuscular substrates were determined. Leg oxygen uptake was similar in the two groups during exercise. In SCI, but not in C, plasma FFA and FFA appearance rate fell during exercise, and plasma glycerol increased less than in C (P < 0.05). Fractional uptake of FFA across the working legs decreased from rest to exercise in all individuals (P < 0.05) but was always lower in SCI than in C (P < 0.05). From rest to exercise, leg FFA uptake increased less in SCI than in C subjects (14 +/- 3 to 57 +/- 20 vs. 41 +/- 13 to 170 +/- 57 micromol x min(-1) x leg(-1); P < 0.05). Muscle glycogen breakdown, leg glucose uptake, carbohydrate oxidation, and lactate release were higher (P < 0.05) in SCI than in C during exercise. Counterregulatory hormonal changes were more pronounced in SCI vs. C, whereas insulin decreased only in C. In conclusion, FFA mobilization, delivery, and fractional uptake are lower and muscle glycogen breakdown and glucose uptake are higher in SCI patients during electrically induced leg exercise compared with healthy subjects performing voluntary exercise. Apparently, blood-borne mechanisms are not sufficient to elicit a normal increase in fatty acid mobilization during exercise. Furthermore, in exercising muscle, FFA delivery enhances FFA uptake and inhibits carbohydrate metabolism, while carbohydrate metabolism inhibits FFA uptake.

In vivo human lipolytic activity in preperitoneal and subdivisions of subcutaneous abdominal adipose tissue.

We studied eight normal-weight male subjects to examine whether the lipolytic rate of deep subcutaneous and preperitoneal adipose tissues differs from that of superficial abdominal subcutaneous adipose tissue. The lipolytic rates in the superficial anterior and deep posterior subcutaneous abdominal adipose tissues and in the preperitoneal adipose tissue in the round ligament were measured by microdialysis and (133)Xe washout under basal, postabsorptive conditions and during intravenous epinephrine infusion (0.15 nmol. kg(-1). min(-1)). Both in the basal state and during epinephrine stimulation, the superficial subcutaneous adipose tissue had higher interstitial glycerol concentrations than the two other depots. Similarly, the calculated glycerol outputs from the superficial depot were significantly higher than those from the deep subcutaneous and the preperitoneal depots. Thus, it is concluded that the lipolytic rate of the superficial subcutaneous adipose tissue on the anterior abdominal wall is higher than that of the deep subcutaneous adipose tissue on the posterior abdominal wall and that of the preperitoneal adipose tissue in the round ligament.

Insulin action and long-term electrically induced training in individuals with spinal cord injuries.

PURPOSE: Individuals with spinal cord injuries (SCI) have an increased prevalence of insulin resistance and type 2 diabetes mellitus. In able-bodied individuals, training with large muscle groups increases insulin sensitivity and may prevent type 2 diabetes mellitus. However, individuals with SCI cannot voluntarily recruit major muscle groups, but by functional electrical stimulation (FES) they can now perform ergometer bicycle training. METHODS: Ten subjects with SCI (35 +/- 2 yr (mean +/- SE), 73 +/- 5 kg, level of lesion C6--Th4, time since injury: 12 +/- 2 yr) performed 1 yr of FES cycling (30 min x d(-1), 3 d x wk(-1) (intensive training)). Seven subjects continued 6 months with reduced training (1 d x wk(-1) (reduced training)). A sequential, hyperinsulinemic (50 mU x min(-1) x m(-2) (step 1) and 480 mU x min(-1) x m(-2) (step 2)), euglycemic clamp, an oral glucose tolerance test (OGTT), and determination of GLUT 4 transporter protein in muscle biopsies were performed before and after training. RESULTS: Insulin-stimulated glucose uptake rates increased after intensive training (from 4.9 +/- 0.5 mg x min(-1) x kg(-1) to 6.2 +/- 0.6 mg x min(-1) x kg(-1) (P < 0.008) (step 1) and from 9.0 +/- 0.8 mg x min(-1) x kg(-1) to 10.6 +/- 0.8 mg x min(-1) x kg(-1) (P = 0.103) (step 2)). With the reduction in training, insulin sensitivity decreased to a similar level as before training (P > 0.05). GLUT 4 increased by 105% after intense training and decreased again with the training reduction. The subjects had impaired glucose tolerance before and after training, and neither glucose tolerance nor insulin responses to OGTT were significantly altered by training. CONCLUSIONS: Electrically induced bicycle training, performed three times per week increases insulin sensitivity and GLUT 4 content in skeletal muscle in subjects with SCI. A reduction in training to once per week is not sufficient to maintain these effects. FES training may have a role in the prevention of the insulin resistance syndrome in persons with SCI.

Effect of force development on contraction induced glucose transport in fast twitch rat muscle.

A previous study has shown that in fast twitch frog sartorius muscle contraction stimulated glucose transport depends only on stimulation frequency and not on workload. In contrast, we have recently shown that in rat slow twitch muscle stimulated to contract at constant frequency, glucose transport varies directly with force development and, in turn, metabolism. The present study was carried out to clarify whether the discrepancy between the earlier studies reflected differences in physiological behaviour between fast and slow twitch muscle. We investigated the effect of force development on glucose transport in incubated fast twitch rat flexor digitorum brevis (rich in type 2a fibres) and epitrochlearis (rich in type 2b fibres) muscle. Muscles were electrically stimulated to perform repeated tetanic contractions at 1 Hz for 10 min. Resting length was adjusted to achieve either no force or maximum force. Glucose transport (2-deoxyglucose uptake) increased when force was produced compared with when it was not (P < 0.05) in both flexor digitorum brevis (19 +/- 7 (basal), 163 +/- 14 (no force) and 242 +/- 17 (max force) nmol x g(-1) x 5 min(-1)) and epitrochlearis (60 +/- 4 (basal), 100 +/- 7 (no force) and 125 +/- 6 (max force) nmol x g(-1) x 5 min(-1)). In both muscles glucose transport increased in parallel with metabolic rate, as reflected by muscle lactate concentrations and 5' AMP-activated protein kinase activity, during contractions. In conclusion, as previously shown for rat soleus muscle, at a given stimulation frequency glucose transport varies directly with force development in rat flexor digitorum brevis and epitrochlearis muscle. Accordingly, force development enhances glucose transport in all mammalian muscle fibre types. The influence of force development probably reflects effects of enhanced 5' AMP-activated protein kinase activity resulting from reduced intra-cellular energy status and pH.

Leg uptake of calcitonin gene-related peptide during exercise in spinal cord injured humans.

Exercise-induced increases in cardiac output (CO) and oxygen uptake (VO2) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function - such as calcitonin gene related peptide (CGRP) - may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 +/- 2 min to fatigue. Voluntary cycling performed both at VO2 similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33.8 +/- 3.1 pmol l(-1) (rest) to 39.5 +/- 4.3 (14%, P<0.05)) with a mean extraction over the working leg of 10% (P<0.05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33.2 +/- 3.8 to 46.9 +/- 3.6 pmol l-1, P<0.05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0.05). The exercise induced increase in leg blood flow was 10-12 fold in both spinal cord injured and controls at similar VO2 (P<0.05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 +/- 7 to 132 +/- 15 bpm) compared with controls and tetraplegics (P<0.05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.