Altered skeletal muscle glucose transport and blood lipid levels in habitual cigarette smokers

We determined whether habitual cigarette smoking alters insulin-stimulated glucose transport and GLUT4 protein expression in skeletal muscle. Vastus lateralis muscle was obtained from 10 habitual cigarette smokers and 10 control subjects using an open muscle biopsy procedure. Basal 3-O-methylglucose transport was twofold higher (P > 0·01) in muscle from habitual smokers (0·05 ± 0·08 vs. 1·04 ± 0·19 μmol ml^?1 h^?1; controls vs. smokers respectively). Insulin (600 pmol l^?1) increased glucose transport 2·6-fold (P > 0·05) in muscle from control subjects, whereas no significant increase was noted in habitual smokers. Skeletal muscle GLUT4 protein expression was similar between the groups. FFA levels were elevated in the smokers (264 ± 49 vs. 748 ± 138 μmol l^?1 for control subjects vs. smokers; P < 0·05), and serum triglyceride levels were increased in the smokers (0·9 ± 0·2 vs. 2·3 ± 0·6 mmol l^?1 for control subjects vs. smokers; P < 0·05). Skeletal muscle carnitine palmitil (acyl) transferase activity was similar between the groups, indicating that FFA transport into the mitochondria was unaltered by cigarette smoking. In conclusion, cigarette smoking appears to have a profound effect on glucose transport in skeletal muscle. Basal glucose transport is markedly elevated, whereas insulin-stimulated glucose transport is impaired. These changes cannot be explained by altered protein expression of GLUT4, but may be related to increased serum FFA and triglyceride levels. These findings highlight the importance of identifying habitual cigarette smokers in studies aimed at assessing factors that lead to alterations in lipid and glucose homeostasis in people with non-insulin-dependent diabetes mellitus (NIDDM).     

Glucose turnover and intima media thickness of internal carotid artery in type 2 diabetes offspring

Background First‐degree offspring (OFF) of type 2 diabetic (T2DM) patients bear a ~40% lifetime risk of developing T2DM. They are insulin resistant and carry a risk of premature atherosclerosis, the extent of which can be estimated by intima media thickness (IMT) of the carotid artery (CA). Thus, this study examines parameters of glucose and lipid metabolism, insulin sensitivity, beta cell function (BCF) and IMT with their interrelationships in middle‐aged OFF. Materials and methods T2DM‐OFF (n = 18, 14f/4m, 45·6 ± 2·1 years, BMI: 26 ± 1 kg m^?2) were compared with 18 matching humans without a family history of diabetes (CON; 14f/4m, 44·5 ± 2·1 years, BMI: 24 ± 1 kg m^?2; each P > 0·30), all with normal glucose tolerance as tested by three‐hour (75 g) oral glucose tolerance tests (OGTT). Two‐hour hyperinsulinaemic (40 mU min^?1·m^?2)isoglycaemic clamp tests were performed with simultaneous measurement of endogenous glucose (D‐[6,6‐²H₂]glucose) production (EGP). IMT [internal (ICA), common CA, and bulb] were measured sonographically. BCF was assessed by Adaptation Index (AI). Results Before and during OGTT, both groups were similar in plasma glucose, insulin, C‐peptide and free fatty acids (FFA), whereas OFF showed ~30% lower (P < 0·03) fasting plasma triglycerides before OGTT. During hyperinsulinaemic clamps, insulin sensitivity was ~38% lower (P < 0·03) in OFF who showed higher plasma FFA (44 ± 9 µmol L^?1) than CON (26 ± 3 µmol L^?1, P < 0·05) after 90 min. EGP was similar in both groups. OFF had 38% (P < 0·007) reduced AI. ICA‐IMT was ~18% higher in OFF (P < 0·002), but did not correlate with insulin sensitivity. Conclusion The data obtained show middle‐aged T2DM‐OFF with normal glucose tolerance displaying reduced total insulin sensitivity and impaired beta cell function, which relates to impaired insulin‐dependent suppression of plasma FFA and increased ICA‐IMT.     

Interstitial lactate levels in human skin at rest and during an oral glucose load: a microdialysis study

In vitro data have suggested that the skin is a significant lactate source. The purpose of the present study was to measure lactate and glucose concentrations in intact human skin in vivo using the microdialysis technique. Microdialysis fibres of 216 μm were inserted intradermally and perfused at a rate of 3 μl min^–1. In the first experimental protocol, dialysis fibres were calibrated by the method of no net flux in eight subjects. Skin lactate concentrations of 2·48 ± 0·17 mmol l^–1 were significantly greater than lactate concentrations of 0·84 ± 0·15 mmol l^–1 in venous plasma (P<0·01). Glucose concentrations in skin and venous plasma were similar (5·49 ± 0·18 vs. 5·26 ± 0·24 mmol l^–1). In the second experimental protocol, changes in lactate and glucose levels were studied in 10 subjects after an oral glucose tolerance test (OGTT). After the OGTT, plasma glucose and lactate levels increased by 54% and 39% to peak levels at 30 and 60 min respectively. In comparison, skin glucose and lactate increased by 41% and 18% at 60 and 90 min. No changes in skin blood flow were observed during the OGTT. The data suggest that resting skin is a significant lactate source with no significant lactate production during OGTT. The cellular source of lactate in the skin remains undetermined to date.     

Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

Aim: During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before and during leg exercise. Material and methods: Eight healthy male subjects were investigated twice in the fasting state: during 3 h infusion of octreotide [30 ng (kg min)^?1] or sodium chloride with exercise at 50% of maximal VO₂ in the last hour. Glucose uptake and oxygen uptake in the leg were measured using Fick’s principle by blood sampling from an artery and a femoral vein. Blood flow in the leg was measured using the indicator (indocyanine green) dilution technique. Results: After an initial decrease during rest, octreotide infusion resulted in a significant increase in arterial glucose concentrations compared to control conditions during exercise (mean ± SEM: 7·6 ± 0·6 versus 5·6 ± 0·1 mmol l^?1, P<0·01). During rest, octreotide did not change the leg glucose uptake (59 ± 10 versus 55 ± 11 μmol min^?1). In contrast, leg glucose uptake was significantly lower during exercise compared to control conditions (208 ± 79 versus 423 ± 87 μmol min^?1, P<0·05). During exercise, leg oxygen uptake was not different in the two experiments (20·4 ± 1·3 versus 19·5 ± 1·1 μmol min^?1). Conclusion: In conclusion, infusion of octreotide reduced leg glucose uptake during exercise, despite the same leg oxygen consumption and blood flow compared to control conditions. The hyperglycaemic effect of octreotide can partly be explained by the reduction in leg glucose uptake. Furthermore, the results suggest that a certain level of circulating insulin is necessary to obtain sufficient stimulation of glucose uptake in the exercising muscles.     

Controlled oral glucose tolerance test: evaluation of insulin resistance with an insulin infusion algorithm that forces the OGTT glycaemic curve within the normal range. A feasibility study

This is a technical study to show the feasibility of a computer-controlled oral glucose tolerance test (OGTT) using a specific algorithm, consisting of an OGTT carried out while insulin is infused as required to keep glycaemia within the normal range ( 30 criteria). This technique allows (a) the amount of insulin (insulin area) required to maintain a normal glycaemic curve to be assessed, a parameter indicating the degree of insulin resistance; and (b) the unique parameter consisting of the insulin secretory response (C-peptide) to a normal glycaemic curve under the inhibitory feedback exerted by the insulin levels required to maintain normal glycaemia to be obtained. Preliminary results confirmed the feasibility of this approach by showing that during the test while the glycaemic area was kept normal the insulinaemic area (endogenous + infused insulin) increased markedly in obese (n = 8) and obese diabetic (n = 5) subjects compared with normal subjects (n = 6), with values of 145·10 ± 26·71, 204·75 ± 20·77 and 68·25 ± 5·93 nmol l^?1 min^?1 respectively (P < 0·01 in both instances). In contrast, endogenous insulin secretion (C-peptide levels) remained almost unchanged. Compared with data in normal subjects, free fatty acid (FFA) values were basally elevated in the obese and obese diabetic patients, and underwent a smaller decrease during the test. The FFA areas were greater than normal in both groups of patients, suggesting that FFAs were not fully suppressible despite the highest possible insulin levels (higher insulin levels would produce hypoglycaemia). The computer-controlled OGTT might be useful for the metabolic study of patients in the clinical setting.     

Plasma lipolytic activity and substrate oxidation after intravenous administration of heparin and a low molecular weight heparin fragment

Summary. This study examines the effects of heparin and a low molecular weight heparin (LMWH) fragment on plasma lipolytic activity and substrate oxidation. Indirect calorimetry was performed continuously in healthy male subjects receiving a constant infusion of fat emulsion (0·2 g min^-1) and glucose (0·8 g min^-1) during a period of 4 h. After 2 h an infusion of heparin (n= 6) or LMWH (n= 6) (100 antifactor Xa units kg^-1) or saline (n= 6) was given over 1 h. Plasma concentration of the fat emulsion decreased by 76 ± 5% with heparin and by 12 ± 7% with LMWH (P<0·01). In the case of LMWH the initial fall was followed by a consistent rise in fat emulsion concentration for the entire remaining study period. Compared to the control experiments, plasma FFA increased five times with heparin and three times with LMWH (P<0·05). The average respiratory quotient (RQ) and energy expenditure (EE) increased constantly during the study period and did not differ significantly between the groups. In all groups the average increase in glucose oxidation was 40–50%, while fat oxidation decreased to a comparable extent. Infusions of heparin and LMWH had no effect on RQ or EE. A microcalorimetric study on isolated rat adipocytes in buffer solutions containing glucose, fat emulsion, heparin or LMWH was also made. The heat output from the adipocytes was not influenced by the presence of heparin or LMWH. In conclusion, infusion of heparin resulted in a pronounced increase in FFA availability, whereas LMWH exerted a less marked lipolytic effect. However, the heparin-induced elevations in plasma FFA were not accompanied by measurable rises in lipid oxidation rate.     

Effect of bicycle exercise on insulin absorption and subcutaneous blood flow in the normal subject

Summary. Elimination of 8 units ¹²⁵I-insulin and ^99mTc-pertechnetate from a subcutaneous depot on the thigh or the abdomen was studied at rest and during intense bicycle exercise in healthy postabsorptive volunteers. Disappearance rates of the tracers as well as plasma insulin and glucose concentrations were determined before, during and after the 20 min exercise period, and compared to corresponding values obtained during a non-exercise, control study on another day. Leg exercise caused a two-fold increase in the rate of ¹²⁵I-insulin disappearance from a leg depot (first-order rate constants rose from 0·68 ± 0·15 to 1·12 ± 0·12%·min^-1, P <0·05), but had no significant effect on the rate of disappearance from an abdominal depot (rate constants were 0·75 ±0·17 and 0·87±0·18%·min^-1 at rest and during exercise, respectively). ^99mTc-pertechnetate clearance from leg or abdomen showed no significant change during exercise, indicating that subcutaneous blood flow was unaltered. Leg, but not abdominal, injection of insulin was associated with a greater rise in plasma insulin during exercise than at rest. The average difference between exercise and control insulin area-under-curve in the leg group (1426 ± 594%·min) was significantly greater (P <0·05) than that from the abdominal group (298 ±251%· min). When the data from the two study groups were pooled, a direct relationship was found to exist between the change in ¹²⁵I-insulin disappearance rate and the change in plasma insulin concentration (r=0·61, P <0·02). Plasma glucose levels fell throughout the observation period both during the exercise and the control study, following leg as well as abdominal injection. The glucose decremental area was greater during exercise than at rest both following leg (P <0·05) and abdominal injection (P <0·01). The exercise-induced mean reduction in plasma glucose was 60% lower following abdominal injection, but this difference was not significant.     

Interactions of stress hormones on lipid and carbohydrate metabolism in man with partial insulin deficiency

Abstract. The metabolic responses to 4-h infusions of adrenaline (3 μg kg^-1 h^-1) and cortisol (10 mg m^-2 h^-1 for 2 h followed by 5 mg m^-2 h^-1 for 2 h), separately and in combination, have been studied in six healthy subjects with concurrent somatostatin infusion (250 μg h^-1). A combined infusion of adrenaline, cortisol, glucagon (180 ng kg^-1 h^-1) and somatostatin has also been studied. Somatostatin plus adrenaline and somatostatin plus cortisol resulted in hyperglycaemia (at 240 min, somatostatin plus adrenaline 11·4 ± 0·4 mmol l^-1, P < 0·001; somatostatin plus cortisol 6·7 ± 0·3 mmol l^-1, P < 0·05; somatostatin alone 4·9 ± 0·4 mmol l^-1). No synergistic effect on blood glucose was seen with adrenaline and cortisol together. When glucagon was added, blood glucose rose more rapidly than without glucagon (9·3 ± 0·4 mmol l^-1v. 7·2 ± 0·5 mmol l^-1 at 45 min, P < 0·001), but plateau values were similar. Plasma NEFA levels were raised by somatostatin plus adrenaline (0·55 ± 0·04–1·82 ± 0·11 mmol l^-1 at 60 min). Somatostatin plus cortisol had no more effect on plasma NEFA than somatostatin alone. During the combined infusion of somatostatin plus adrenaline plus cortisol, a synergistic effect on plasma NEFA was observed (2·30 ± 0·11 mmol l^-1 at 60 min, P < 0·01 v. somatostatin plus adrenaline). This occurred despite a small escape of insulin secretion. The lipolytic actions of adrenaline are potentiated by elevated circulating cortisol levels in insulin-deficient man. Glucagon does not modify this response, but accelerates the development of hyperglycaemia.     

Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance

Abstract. In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [¹³C]bicarbonate (0·1 mg kg^-1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO_2max on three separate occasions. Elimination of CO₂ from labelled bicarbonate was 62·6±8·1% at rest, 103·6±11·3% during exercise (P<0·01) and 43·0±4·7% during recovery from exercise (P= 0·01). During exercise mean residence time (MRT) was shorter than at rest (35±7 min vs. 54±9min, P < 0·02) and CO₂ pool size was larger (998±160 ml CO₂kg^-1, vs. 194±28ml CO₂kg^-1, P < 0·001). Compared to values obtained at rest, during recovery from exercise, MRT and CO₂ pool size were reduced (34±5min, P < 0·05; 116±19 ml CO₂kg^-1, P < 0·02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [¹³C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46·1±5·6%, P < 0·01) but was unaltered (50·9±5·6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO₂ pool size decreased (37±3min, P<0·01 and 123±10ml CO₂kg^-1, P < 0·01, respectively) whereas in alkalosis MRT was unchanged (65±8 min NS) but CO₂ pool size was increased (230±23ml CO₂kg^-1, P < 0·05). The kinetics of elimination of ¹³CO₂ from administered bicarbonate after exercise are different to those at rest and resemble acidosis. The appropriate correction factor for sequestered ¹³C should be used in metabolic studies of the post-exercise state when using ¹³C tracers.     

The effect of different exercise‐testing protocols on atrial natriuretic peptide

The aim of this study was to examine and to compare alterations in the secretion of atrial natriuretic peptide (ANP) during different exercise‐testing protocols in moderately trained men. Fifteen healthy male physical education students were studied (mean age 22·3 ± 2·5 years, training experience 12·3 ± 2·5 years, height 1·80 ± 0·06 m, weight 77·4 ± 8·2 kg). Participants performed an initial graded maximal exercise testing on a treadmill for the determination of VO_2max (duration 7·45–9·3 min and VO_2max 55·05 ± 3·13 ml kg^?1 min^?1) and were examined with active recovery (AR), passive recovery (PR) and continuous running (CR) in random order. Blood samples for plasma ANP concentration were taken at rest (baseline measurement), immediately after the end of exercise as well as after 30 min in passive recovery time (PRT). The plasma ANP concentration was determined by radioimmunoassay (RIA). The results showed that ANP plasma values increased significantly from the rest period to maximal values. In the short‐term graded maximal exercise testing the ANP plasma values increased by 56·2% (44·8 ± 10·4 pg ml^?1 versus 102·3 ± 31·3 pg ml^?1, P<0.001) and in the CR testing the ANP levels increased by 29·2% (44·8 ± 10·4 pg ml^?1 versus 63·3 ± 19·8 pg ml^?1, P<0.001) compared to the baseline measurement. Moreover, the values of ANP decreased significantly (range 46·4–51·2%, P<0.001) in PRT after the end of the four different exercise modes. However, no significant difference was evident when ANP values at rest and after AR and PR were compared. It is concluded that the exercise testing protocol may affect the plasma ANP concentrations. Particularly, short‐term maximal exercise significantly increases ANP values, while the intermittent exercise form of active and passive recovery decreases ANP concentrations.     

Effects of physical exercise on insulin absorption in insulin-dependent diabetics. A comparison between human and porcine insulin

Summary. Nine insulin-dependent diabetics with undetectable plasma C-peptide (<0·05 nmol 1^-1) and without insulin antibodies (insulin binding to IgG<0·05 Ul^-1) received subcutaneous injections of 10 U ¹²⁵I-labelled soluble human or porcine insulin in the thigh on 2 consecutive days. Disappearance rates of ¹²⁵I were monitored continuously by external counting and plasma insulin levels were determined during rest for 30 min, bicycle exercise of moderate intensity for 40 min, and 60 min recovery. Subcutaneous blood flow was measured concomitantly in the contralateral thigh by the ¹³³Xenon clearance technique. During the initial period of rest human insulin was absorbed approximately 40% faster than its porcine analogue (first order rate constants 0·37±0·06 vs 0·27±0·06% min^-1, P<0·05) and the increment of the area under the plasma insulin curve was greater after hum-ii than after porcine insulin (184±46 vs 112±42 mUl^-1 min, P<0·05). Exercise enhanced the absorption rates for both ¹²⁵I-insulins to 0·50±0·06 and 0·48±0·10% min^-1 for human and porcine insulin, respectively (P<0·05). This increase was less pronounced for human compared to porcine insulin (49±19 vs 105±40%, P=0·06). During exercise plasma insulin rose to 37±5 mUl^-1 after human and 30±5 mUl^-1 after porcine insulin and the areas under the plasma insulin curves were similar. During the recovery phase the absorption rates decreased slightly compared to the exercise value for both insulins. The blood glucose lowering effect was similar for the two insulins. Subcutaneous blood flow was not significantly altered by exercise in either group. It is concluded that during rest human soluble insulin is more rapidly absorbed than porcine insulin. Physical exercise tends to increase porcine insulin absorption more and eliminates the basal difference in the absorption kinetics between human and porcine insulin. The increased insulin absorption during exercise is not coupled to corresponding changes in the subcutaneous blood flow.     

The exercise heart rate profile in master athletes compared to healthy controls

Endurance exercise protects the heart via effects on autonomic control of heart rate (HR); however, its effects on HR indices in healthy middle‐aged men are unclear. This study compared HR profiles, including resting HR, increase in HR during exercise and HR recovery after exercise, in middle‐aged athletes and controls. Fifty endurance‐trained athletes and 50 controls (all male; mean age, 48·7 ± 5·8 years) performed an incremental symptom‐limited exercise treadmill test. The electrocardiographic findings and HR profiles were evaluated. Maximal O₂ uptake (52·6 ± 7·0 versus 34·8 ± 4·5 ml kg^?1 min^?1; P<0·001) and the metabolic equivalent of task (15·4 ± 1·6 versus 12·2 ± 1·5; P<0·001) were significantly higher in athletes than in controls. Resting HR was significantly lower in athletes than in controls (62·8 ± 6·7 versus 74·0 ± 10·4 beats per minute (bpm), respectively; P<0·001). Athletes showed a greater increase in HR during exercise than controls (110·1 ± 11·0 versus 88·1 ± 15·4 bpm; P<0·001); however, there was no significant between‐group difference in HR recovery at 1 min after cessation of exercise (22·9 ± 5·6 versus 21·3 ± 6·7 bpm; P = 0·20). Additionally, athletes showed a lower incidence of premature ventricular contractions (PVCs) during exercise (0·0% versus 24·0%; P<0·001). Healthy middle‐aged men participating in regular endurance exercise showed more favourable exercise HR profiles and a lower incidence of PVCs during exercise than sedentary men. These results reflect the beneficial effect of endurance training on autonomic control of the heart.     

Minimal model analyses of insulin sensitivity and glucose-dependent glucose disposal in black and white Americans: a study of persons at risk for type 2 diabetes

Abstract. We have examined the impact of race and positive family history of type 2 diabetes on glucose/insulin dynamics and the two components of glucose disposal in healthy, first-degree relatives of black and white American patients with type 2 diabetes mellitus who are at a greater risk from the disease and their healthy control subjects. Seventeen black and 15 white relatives were studied. Twenty-two black people and 24 white people, without family history of type 2 diabetes, served as healthy control subjects. Standard oral glucose tolerance test (OGTT) and tolbutamide-modified frequent sampling intravenous glucose tolerance (FSIGT) tests were performed in each subject. Insulin sensitivity index (S_I) and glucose effectiveness (S_G) were calculated using the MINI-MOD method described by Bergman et al. Mean fasting and post-stimulation serum glucose levels were not significantly different in the black and white relatives. However, mean serum insulin responses to oral and/or intravenous stimulation were significantly greater in the blacks than whites, irrespective of positive family history of diabetes. The mean S_I was significantly (P < 0·02) lower (52%) in the black (3·67±0·56) than the white [7·50±1·93 times 10^-4 min^-1 (mUl)^-1] relatives. Comparing the healthy controls, the mean S_I was significantly (P < 0·02) lower (51%) in black than white controls (4·84±0·78 vs. 9·71±1·27 times 10min^-1(mUl)^-1]. Mean S_G and K_G were greater (P < ·05) in the blacks than whites, irrespective of family history of diabetes. In summary, the present study demonstrates that non-diabetic black people manifest insulin resistant and hyperinsulinaemia, irrespective of family history of diabetes, when compared to white people. We speculate that these metabolic changes could play a potential role in the higher prevalence of type 2 diabetes in the black Americans.     

Restoration of peak vascular conductance after simulated microgravity by maximal exercise

We sought to determine if (i) peak vascular conductance of the calf was reduced following prolonged exposure to simulated microgravity, and (ii) if maximal cycle ergometry performed at the end of microgravity exposure stimulated a restoration of peak calf vascular conductance. To do this, peak vascular conductance of the calf was recorded following ischaemic plantar flexion exercise to fatigue in seven men after 16 days of head-down tilt (HDT) under two conditions: (i) after one bout of maximal supine cycle ergometry completed 24 h prior to performance of ischaemic plantar flexion exercise, and (ii) in a control (no cycle ergometry) condition. Following HDT, peak vascular conductance was reduced in the control condition (0·38 ± 0·02 to 0·24 ± 0·02 ml 100 ml^?1 min^?1 mmHg^?1; P = 0·04), but was restored when subjects performed cycle ergometry (0·33 ± 0·05 to 0·28 ± 0·04 ml 100 ml^?1 min^?1 mmHg^?1; P = 0·46). After HDT, time to fatigue during ischaemic plantar flexion exercise was not different from pre-HDT 24 h after performance of exhaustive cycle ergometry (120 ± 24 vs. 122 ± 19 s), but was decreased in the control condition (116 ± 11 vs. 95 ± 8 s; P = 0·07). These data suggest that a single bout of maximal exercise can provide a stimulus to restore peak vascular conductance and maintain time to fatigue during performance of ischaemic plantar flexion exercise.     

Positive effect of exercise training at maximal fat oxidation intensity on body composition and lipid metabolism in overweight middle‐aged women

The purpose of this study was to test the hypothesis that 10 weeks of supervised exercise training at the maximal fat oxidation (FATmax) intensity would improve important variables of body composition and lipid metabolism in overweight middle‐aged women. A longitudinal study design was employed to evaluate the effects of FATmax exercise training. Thirty women (45–59 years old; BMI 28·2 ± 1·8 kg m^?2; body fat 38·9 ± 4·1%) were randomly allocated into the Exercise and Control groups, n = 15 in each group. Body composition, FATmax, predicted VO₂max, lipid profile, plasma lipoprotein lipase activity and serum leptin concentration were measured before and after the experimental period. The Exercise group was trained at the individualized FATmax intensity, 5 days per week and 1 h per day for 10 weeks. No diet control was introduced during the experimental period for all participants. Exercise group obtained significant decreases in body mass, BMI, body fat % and abdominal fat mass, as well as the concentrations of triglycerides, serum leptin and blood glucose. The activity of lipoprotein lipase was increased in trained participants. There were no changes in these variables in the Control group. In addition, there was no significant change in daily energy intake for all participants before and after the experimental period. In conclusion, the 10‐week FATmax exercise training achieved improvements in body composition and lipid metabolism in overweight middle‐aged women. This result suggests FATmax is an effective exercise training intensity for obesity treatment.     

Influence of glucose and fructose ingestion on the capacity for long-term exercise in well-trained men

Summary. The aim of the present study was to examine the influence of glucose and fructose ingestion on the capacity to perform prolonged heavy exercise. Eight well-trained healthy volunteers exercised on a bicycle ergometer at 68±3% of their VO₂ max until exhaustion, on three occasions, with 8-day intervals. During the exercise they ingested either glucose (250 ml, 7%), fructose (250 ml, 7%) or water (250 ml) every 20 min in a double-blind randomized study design. Arterial blood samples were collected at rest and during exercise for the determination of substrates and hormones. Muscle glycogen content (m. quadriceps femoris) was measured before and after exercise. The duration of exercise lengthened with repeated exercise (3rd test: 136±13 min v. 1st test: 110±12 min, P<0·01). Corrected for the sequence effect, total work time until exhaustion was significantly longer with glucose (137±13 min) than with either fructose (114±12 min) or water (116±13 min) (both P<0·01). When glucose or fructose was ingested, the arterial plasma glucose concentration was maintained at the normoglycaemic level; with water ingestion, plasma glucose values fell during exercise in seven subjects and remained at the resting level in the eighth subject. The muscle glycogen concentration was 467±29 mmol kg d.w.^-1 at rest and fell to approximately half the initial value at exhaustion. In the subgroup of seven subjects in whom glucose values decreased with water intake, the mean rate of glycogen degradation was significantly lower (P<0·05) with the ingestion of glucose (1·3±0·4 mmol kg d.w.^-1 min^-1) as compared to fructose (2·1±0·5 mmol kg d.w.^-1 min^-1) or water (2·3±0·5 mmol kg d.w.^-1 min^-1). Intermittent glucose ingestion (3×17·5 g h^-1) during prolonged, heavy bicycle exercise postpones exhaustion and exerts a glycogen-conserving effect in the working muscles. In contrast, fructose ingestion during exercise maintains the glucose concentration at the basal level but fails to influence either muscle glycogen degradation or endurance performance.     

Acute effects of aerobic exercise intensity on arterial stiffness after glucose ingestion in young men

Arterial stiffness increases after glucose ingestion. Acute low‐ and moderate‐intensity aerobic exercise decreases arterial stiffness. However, the acute effects of 30 min of cycling at low‐ and moderate‐intensity [25% (LE trial) and 65% (ME trial) peak oxygen uptake, respectively] on arterial stiffness at 30, 60 and 120 min of a postexercise glucose ingestion. Ten healthy young men (age, 22·4 ± 0·5 years) performed LE and ME trials on separate days in a randomized controlled crossover fashion. Carotid–femoral (aortic) pulse wave velocity (PWV), femoral–ankle (leg) PWV, carotid augmentation index (AIx) and carotid blood pressure (BP) (applanation tonometry), brachial and ankle BP (oscillometric device), heart rate (HR) (electrocardiography), blood glucose (UV‐hexokinase method) and blood insulin (CLEIA method) levels were measured at before (baseline) and at 30, 60 and 120 min after the 75‐g OGTT. Leg PWV, ankle pulse pressure and BG levels significantly increased from baseline after the 75‐g OGTT in the LE trial (P<0·05), but not in the ME trial. Insulin levels and HR significantly increased from baseline after the 75‐g OGTT in both trials (P<0·05). Aortic PWV, carotid AIx, brachial BP and carotid BP did not change from baseline after the 75‐g OGTT in both trials. The present findings indicate that aerobic exercise at moderate intensity before glucose ingestion suppresses increases leg arterial stiffness after glucose ingestion.     

Effects of intense exercise training on endothelium-dependent exercise-induced vasodilatation

To determine whether intense exercise training affects exercise-induced vasodilatation, six subjects underwent 4 weeks of handgrip training at 70% of maximal voluntary contraction. Exercise forearm vascular conductance (FVC) responses to an endothelium-dependent vasodilator (acetylcholine, ACH; 15, 30, 60 μg min^?1) and an endothelium-independent vasodilator (sodium nitroprusside, SNP; 1·6, 3·2, 6·4 μg min^?1) and FVC after 10 min of forearm ischaemia were determined before and after training. Training elicited significant (P<0·001) increases in grip strength (43·4 ± 2·3 vs. 64·1 ± 3·5 kg, before vs. after, mean ± SEM), forearm circumference (26·7 ± 0·4 vs. 27·9 ± 0·4 cm) and maximal FVC (0·4630 ± 0·0387 vs. 0.6258 ± 0·0389 units, P<0·05). Resting FVC did not change significantly with training (0·0723 ± 0·0162 vs. 0.0985 ± 0·0171 units, P>0·4), but exercise FVC increased (0·1330 ± 0·0190 vs. 0.2534 ± 0·0387 units, P<0·05). Before and after the training, ACH increased exercise FVC above the control (no drug) exercise FVC, whereas SNP did not. Training increased (P<0·05) the exercise FVC responses to ACH (0·3344 ± 0·1208 vs. 0.4303 ± 0·0858 units, before vs. after training, 60 μg min^?1) and SNP (0·2066 ± 0·0849 vs. 0.3172 ± 0·0628 units, 6·4 μg min^?1). However, these increases were due to the increase in control (no drug) exercise FVC, as the drug-associated increase in exercise FVC above control did not differ between trials (P>0·6). These results suggest that exercise FVC is increased by both exercise training and stimulating the release of endothelium-dependent vasodilators. However, training does not affect the vascular response to these vasodilators.     

Post-exercise cutaneous hyperaemia resulting from local exercise of an extremity

Large changes in skin blood flow occur after exercise. Most studies have concentrated on the systemic effects of vigorous exercise on skin blood flow. We were interested in the post-exercise response in the neighbourhood of focal exercise. We used a painless neuromuscular electronic stimulator to exercise the muscles of the forearm, producing flexion of the fingers. There was no change in blood pressure and only a small increase in heart rate during this exercise. We measured blood flow during a 5-min pre-exercise period and a 5-min post-exercise period at the forearm, at the dorsum of the index finger and on the pad of the index finger. We also measured values on the contralateral non-exercised extremity during exercise as well as during matched time periods in control experiments with no exercise. Exercise did elicit an increased blood flow in the post-exercise period at all three sites compared with the control experiments with no exercise and on the contralateral extremity. For example, the increase in blood flow at the finger dorsum was 2.1±0.1 ml (min 100 g)^?1 after exercise compared with ?0.08±0.09 ml min^?1 100 g^?1 during the control experiment and 0.1±0.1 ml (min 100 g)^?1 on the contralateral arm (all P<0.01). The local application of heat at the site of blood flow monitoring produced a substantial increase in the post-exercise response at the two finger locations [27.4±0.4 ml (min 100g)^?1 at the finger dorsum], but not at the arm. This is the first demonstration that highly focal exercise, unaccompanied by a systemic haemodynamic response, can elicit a post-exercise cutaneous hyperaemia. Local heating produced a large synergistic increase in the post-exercise hyperaemia at sites with arteriovenous microvascular perfusion but not at sites with primarily nutritive perfusion. These findings show that local vasoregulatory changes occur in response to exercise, even in the absence of whole-body haemodynamic and thermal change.     

Insulin sensitivity in alcoholic cirrhosis

The amount-of-substance rate of glucose metabolism and its sensitivity to the concentration of insulin was quantified in 10 non-diabetic patients with alcoholic cirrhosis of varying severity, using the ‘glucose clamp technique’. Fasting glucose and insulin were 5.4±0.3 mmol/1 and 187±50 μmol/1 (mean ± SEM), respectively. During the hyperglycaemic clamp (blood glucose at 12.5 mmol/1) the glucose metabolic rate (divided by body mass) was 27± 4 μmol·min^?1·kg^?1 at an insulin concentration of 998± 158 pmol/1. Thus the insulin sensitivity of the tissue glucose metabolism was 22±7 m³·min^?1·kg^?1. During the euglycaemic clamp exogenous insulin was given to a concentration of 574± 72 pmol/1. The resulting glucose metabolic rate was 20± 4 μmol·min^?1·kg^?1 and the insulin sensitivity the same as during hyperglycaemia. The calculated systemic delivery rate of insulin (divided by body surface area) was 783± 172 pmol·min^?1·m^?2. Fasting glucagon was 32± 5 pmol/ and only partly depressed by glucose or insulin. In comparison with stated relevant control groups cirrhotics exhibit glucose intolerance characterized by decreased sensitivity to insulin, hyperinsulinaemia due to increased release, and hyperglucagonaemia with decreased suppressibility. There was no relation between clinical or biochemical data of the patients and the above results, suggesting that the abnormal glucose metabolism does not depend directly on the decreased liver function but on a disturbed pancreatic-hepatic-peripheral axis.