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.

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.

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.

Hemodynamics in diabetic orthostatic hypotension.

Hemodynamic variables (blood pressure, cardiac output, heart rate, plasma volume, splanchnic blood flow, and peripheral subcutaneous blood flow) and plasma concentrations of norepinephrine, epinephrine, and renin were measured in the supine position and after 30 min of quiet standing. This was done in normal subjects (n = 7) and in juvenile-onset diabetic patients without neuropathy (n = 8), with slight neuropathy (decreased beat-to-beat variation in heart rate during hyperventilation) (n = 8), and with severe neuropathy including orthostatic hypotension (n = 7). Blood pressure decreased precipitously in the standing position in the diabetics with orthostatic hypotension, whereas moderate decreases were found in the other three groups. Upon standing, heart rate rose and cardiac output and plasma volume decreased similarly in the four groups. The increases in total peripheral resistance, splanchnic vascular resistance and subcutaneous vascular resistance were all significantly lower (P less than 0.025) in the patients with orthostatic hypotension compared with the other three groups. The increase in plasma norepinephrine concentrations in the patients with orthostatic hypotension was significantly lower (P less than 0.025) than in the patients without neuropathy, whereas plasma renin responses to standing were similar in the four groups. We conclude that in diabetic hypoadrenergic orthostatic hypotension the basic pathophysiological defect is lack of ability to increase vascular resistance, probably due to impaired sympathetic activity in the autonomic nerves innervating resistance vessels; cardiac output and plasma volume responses to standing are similar to those found in normal subjects and in diabetics without neuropathy.

Effect of physical training on glucose transporters in fat cell fractions.

Physical training increases maximally insulin-stimulated glucose assimilation and 3-O-methylglucose transport in epididymal fat cells. In the present report, glucose-inhibitable cytochalasin B binding in subcellular fractions of epididymal adipocytes was measured to assess changes in number of glucose transporters induced by training. Groups of rats trained by swimming were compared to control groups of the same age, matched with respect to body weight by restricted feeding. It was found that in trained rats the number of glucose transporters in the low density microsome fractions from non-insulin-stimulated fat cells was larger than in untrained rats. In both groups of rats, insulin stimulation of adipocytes decreased the number of glucose transporters in low-density microsomes by about 60% and increased the number of glucose transporters in the plasma membrane fractions. The number of glucose transporters in the plasma membrane fractions from maximally insulin-stimulated fat cells was larger in trained rats than in control rats. [U-14C]Glucose incorporation into lipids varied in proportion to plasma membrane cytochalasin B binding per cell under all conditions tested. The results explain the enhancing effect of training on insulin responsiveness transport of hexose in fat cells.

Training increases the concentration of [3H]ouabain-binding sites in rat skeletal muscle.

Exercise is associated with a net loss of K+ from the working muscles and an increased plasma K+ concentration, indicating that the capacity for intracellular reaccumulation of K+ is exceeded. Training reduces the exercise-induced rise in plasma K+, and an increased plasma [K+] may interfere with physical performance. Since the clearing of K+ from the extracellular space depends on the capacity for active K+ uptake in skeletal muscle, the effects of training and inactivity on the total concentration of (Na+ + K+)-ATPase was determined. Following 6 weeks of swim training, the concentration of [3H]ouabain-binding sites in rat hindlimb muscles was up to 46% (P less than 0.001) higher than in those obtained from age-matched controls. Whereas muscle Na+, K+ contents remained unchanged, the concentration of citrate synthase increased by up to 76% (P less than 0.001). Training induced no change in the [3H]ouabain-binding-site concentration in the diaphragm, but in the heart ventricles, the K+-dependent 3-O-methylfluorescein phosphatase activity increased by 20% (P less than 0.001). Muscle inactivity induced by denervation, plaster immobilisation or tenotomy reduced the [3H]ouabain-binding-site concentration by 20-30% (P less than 0.02-0.001) within 1 week. In conclusion, training leads to a significant and reversible rise in the concentration of (Na+ + K+)-ATPase in muscle cells. This may be of importance for the beneficial effects on physical performance by improving the maximum capacity for K+ clearance.

Increased muscle glucose uptake after exercise. No need for insulin during exercise.

It has recently been shown that insulin sensitivity of skeletal muscle glucose uptake and glycogen synthesis is increased after a single exercise session. The present study was designed to determine whether insulin is necessary during exercise for development of these changes found after exercise. Diabetic rats and controls ran on a treadmill and their isolated hindquarters were subsequently perfused at insulin concentrations of 0, 100, and 20,000 microU/ml. Exercise increased insulin sensitivity of glucose uptake and glycogen synthesis equally in diabetic and control rats, but insulin responsiveness of glucose uptake was noted only in controls. Analysis of intracellular glucose-6-phosphate, glucose, glycogen synthesis, and glucose transport suggested that the exercise effect on responsiveness might be due to enhancement of glucose disposal. After electrical stimulation of diabetic hindquarters in the presence of insulin antiserum, insulin sensitivity of 3-O-methylglucose transport was increased to the same extent as in muscle from healthy rats stimulated in the presence of insulin at 50 microU/ml. Furthermore, in muscle depleted of glycogen by contractions, transport of 3-O-methylglucose was increased in the presence of insulin antiserum and in the absence of increased regional perfusate flow. It is concluded that after exercise, increased sensitivity of muscle glucose metabolism to insulin can be found in the absence of insulin during exercise, but still involves increased membrane transport of glucose. At maximal insulin concentrations, the enhancing effect of exercise on glucose uptake may involve enhancement of glucose disposal, an effect that is probably less in muscle from diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Normal effect of insulin to stimulate leg blood flow in NIDDM.

In patients with non-insulin-dependent diabetes mellitus (NIDDM), a decreased effect of insulin in stimulating leg blood flow (LBF) has been reported. We reinvestigated the effect of insulin on LBF and validated our data by use of other measures. Eight healthy men (control group) and seven men with NIDDM were studied (age 59 +/- 1 and 58 +/- 3 years, weight 83 +/- 3 and 86 +/- 6 kg, fat-free mass 66 +/- 1 and 64 +/- 3 kg, respectively [mean +/- SE, all P > 0.05]; body mass index 26 +/- 1 and 29 +/- 1 kg/m2, fasting plasma insulin 72 +/- 7 and 187 +/- 22 pmol/l, fasting plasma glucose 5.8 +/- 0.2 and 10.2 +/- 1.7 mmol/l [all P < 0.05]). A three-step hyperinsulinemic glucose clamp (ambient glucose level) was performed, combined with catheterization of an artery and both femoral veins. Expiratory air was collected, LBF was measured by thermodilution, and blood was sampled and analyzed for oxygen content. Insulin concentration was increased to 416 +/- 22 and 509 +/- 43 (step I), 1,170 +/- 79 and 1,299 +/- 122 (step II), and 15,936 +/- 1,126 and 16,524 +/- 1,916 (step III) pmol/l in control and NIDDM subjects, respectively (P > 0.05). LBF increased similarly (P > 0.05) in the two groups (from 287 +/- 23 and 302 +/- 12 [basal] to 308 +/- 31 and 362 +/- 9 [I], 371 +/- 29 and 409 +/- 17 [II], and 434 +/- 32 and 472 +/- 29 [III] ml.min-1.leg-1 in control and NIDDM subjects, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit insulin resistance and decreased glucose transport in skeletal muscle. Total content of muscle GLUT4 protein is not affected by NIDDM, whereas GLUT4 mRNA content is reported, variously, to be unaffected or increased. Physical training is recommended in the treatment of NIDDM, but the effect of training on muscle GLUT4 protein and mRNA content is unknown. To clarify the effect of training in NIDDM, seven men with NIDDM (58 +/- 2 years of age [mean +/- SE]) and eight healthy men (59 +/- 1 years of age) (control group) performed one-legged ergometer bicycle training for 9 weeks, 6 days/week, 30 min/day. Biopsies were obtained from the vastus lateralis leg muscle before and after training. GLUT4 protein analyses was performed along with analyses of muscle biopsies from five young (23 +/- 1 years of age) (young group), healthy subjects who participated in a previously published identical study. In response to training, maximal oxygen uptake increased (delta 3.3 +/- 1.8 in NIDDM subjects and 4.5 +/- 1.2 ml.min-1.kg-1 in control subjects [both P < 0.05]). Before training, GLUT4 protein content was similar in NIDDM, control, and young subjects (0.35 +/- 0.02, 0.34 +/- 0.03, and 0.41 +/- 0.03 arbitrary units, respectively), and it increased (P < 0.05) in all groups during training (to 0.43 +/- 0.03, 0.40 +/- 0.03, and 0.57 +/- 0.08 arbitrary units, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-stimulated muscle glucose clearance in patients with NIDDM. Effects of one-legged physical training.

Physical training increases insulin action in skeletal muscle in healthy men. In non-insulin-dependent diabetes mellitus (NIDDM), only minor improvements in whole-body insulin action are seen. We studied the effect of training on insulin-mediated glucose clearance rates (GCRs) in the whole body and in leg muscle in seven patients with NIDDM and in eight healthy control subjects. One-legged training was performed for 10 weeks. GCR in whole body and in both legs were measured before, the day after, and 6 days after training by hyperinsulinemic (28, 88, and 480 mU x min(-1) x m(-2)), isoglycemic clamps combined with the leg balance technique. On the 5th day of detraining, one bout of exercise was performed with the nontraining leg. Muscle biopsies were obtained before and after training. Whole-body GCRs were always lower (P < 0.05) in NIDDM patients compared with control subjects and increased (P < 0.05) in response to training. In untrained muscle, GCR was lower (P < 0.05) in NIDDM patients (13 +/- 4, 91 +/- 9, and 148 +/- 12 ml/min) compared with control subjects (56 +/- 12, 126 +/- 14, and 180 +/- 14 ml/min). It Increased (P < 0.05) in both groups in response to training (43 +/- 10, 144 +/- 17, and 205 +/- 24 [NIDDM patients] and 84 +/- 10, 212 +/- 20, and 249 +/- 16 ml/min [control subjects]). Acute exercise did not increase leg GCR. In NIDDM patients, the effect of training was lost after 6 days, while the effect lasted longer in control subjects. Training increased (P < 0.05) muscle lactate production and glucose storage as well as glycogen synthase (GS) mRNA in both groups. We conclude that training increases insulin action in skeletal muscle in control subjects and NIDDM patients, and in NIDDM patients normal values may be obtained. The increase in trained muscle cannot fully account for the increase in whole-body GCR. Improvements in GCR involve enhancement of insulin-mediated increase in muscle blood flow and the ability to extract glucose. They are accompanied by enhanced nonoxidative glucose disposal and increases in GS mRNA. The improvements in insulin action are short-lived.

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)

Interaction of sulfonylureas and exercise on glucose homeostasis in type 2 diabetic patients.

OBJECTIVE: To determine whether the plasma glucose-lowering effects of sulfonylureas and acute submaximal exercise are additive and, accordingly, to determine whether they may increase the risk of hypoglycemia when combined in fasting patients. RESEARCH DESIGN AND METHODS: Eight postabsorptive type 2 diabetic patients were examined at three occasions: after oral sulfonylurea (7 mg glibenclamide), during 60 min of ergometer cycle exercise at 57 +/- 3% of VO2max, and during exercise after glibenclamide. RESULTS: Heart rate, VO2, and lactate responses to exercise were comparable (P > 0.05) on days with and without glibenclamide. Plasma insulin concentrations were always increased by glibenclamide, and they were lowered identically by exercise with and without glibenclamide. However, throughout exercise, absolute concentrations of insulin were lower on days without glibenclamide compared with days with glibenclamide (34.5 +/- 4.7 vs. 47.4 +/- 5.5 pmol/l; P < 0.05). At the start of exercise, glucose concentrations were similar between experiments (P > 0.05). The rate of decrease in glucose during exercise was higher (P < 0.05) on days with both glibenclamide and exercise, compared with days with glibenclamide alone and days with exercise alone (-0.035 +/- 0.009 vs. -0.016 +/- 0.002 and -0.022 +/- 0.005 mmol.l-1.min-1, respectively). Consequently, the glucose nadir was lower on days with glibenclamide and exercise than on days with glibenclamide or exercise alone (6.7 +/- 1.1 vs. 8.1 +/- 0.9 and 7.6 +/- 1.0 mmol/l, respectively; P < 0.05). During exercise, the rate of appearance of plasma glucose determined by 3-[3H]glucose infusion was lower on days with glibenclamide than on days without glibenclamide (2.3 +/- 0.1 vs. 2.9 +/- 0.1 mg.min-1.kg-1; P < 0.05). In contrast, glucose clearance was identical (P > 0.05). CONCLUSIONS: In postabsorptive type 2 diabetic patients, the hypoglycemic action of glibenclamide and exercise is enhanced when the treatments are combined. The interaction reflects an increased inhibition by glibenclamide-enhanced insulin levels of hepatic glucose production when hepatic glucose production is accelerated by exercise.

Prolactin, growth hormone, thyrotropin, 3,5,3'-triiodothyronine, and thyroxine responses to exercise after fat- and carbohydrate-enriched diet.

The effect of 4 days of intake of a fat-enriched (76%) diet (F1 and F2 experiments) or a carbohydrate-enriched (77%) diet (CH experiment) on circulating levels of glucose, insulin, GH, PRL, and thyroid hormones during prolonged exercise was studied in seven healthy males. After each of the three diet periods, the subjects ran on a treadmill at 70% of individual maximal oxygen uptake. At exhaustion, a 10-min rest was allowed, after which the subjects were encouraged to run while glucose (F1 and CH experiments) or glucose and insulin (F2 experiment) concentrations were restored to preexercise levels. The fat diet decreased the mean concentrations of glucose, insulin, and T3 at rest and increased the mean GH level, whereas, mean PRL, T4, and TSH levels were not changed by diet. During exercise, the decline in glucose and insulin concentrations as well as the progressive increase in GH and PRL concentrations in plasma were enhanced by the fat diet compared to the carbohydrate diet (P < 0.02). Plasma concentrations of T4, T3, and TSH were not significantly (P > 0.05) changed during exercise, but at identical times the T3 concentration was significantly (P < 0.05) higher in CH experiments than in F experiments. Glucose or glucose and insulin infusion during continued exercise eliminated hypoglycemic symptoms, and a further small rise in plasma PRL concentration was seen after the fat-enriched diet and glucose infusion (F1 experiment) but not during the F2 and CH experiments. In contrast, GH, TSH, T3, and T4 levels were not significantly (P > 0.05) changed in any of the experiments. These data suggest that glucopenia can be an important modulator of plasma GH and PRL during exercise. Furthermore, it is suggested that GH secretion is more sensitive to a decrease in glucose and insulin levels than PRL secretion.

Twenty-four-hour profile of plasma glucose and glucoregulatory hormones during normal living conditions in trained and untrained men.

Compared with untrained (UT) subjects, in trained (T) subjects the increased insulin sensitivity and decreased glucose induced insulin secretion would tend to promote health by decreasing glucose levels and insulin secretion whereas the increased food intake would tend to increase these variables. To study the net effect of training, blood was sampled from seven T and eight UT young men [VO2max: 76 +/- 2 (T) vs. 48 +/- 1 (UT) mL.kg-1.min-1] for 24 h during ordinary living conditions. Athletes exercised 204 +/- 20 min and ate 50% more calories and 130% more carbohydrate than UT subjects (P less than 0.05). However, 24-h integrated plasma concentrations of glucose, C-peptide, glucagon, free fatty acids, and glycerol as well as glycosylated hemoglobin levels were identical in T and UT subjects. Mean insulin concentration was 41% lower in T than in UT but levels differed significantly (P less than 0.05) only late during the night. Urinary excretion of pancreatic peptides paralleled plasma concentrations. In conclusion, during training adaptations in pancreas- and insulin-sensitive tissues allow the necessary increase in food intake without harmful hyperglycemia and overloading of beta-cells, but sparing of insulin secretion and reductions in glucose levels are only relative to food intake. However, training may be wholesome by increasing hepatic insulin extraction and thereby decreasing arterial insulin levels. Training-induced beta-cell adaptation is not caused by diminished average glucose levels. Finally, renal handling of insulin, C-peptide, and glucagon is not influenced by training.

No response of pancreatic hormones to hypoglycemia in diabetic autonomic neuropathy.

The responses of pancreatic hormones (i.e. glucagon, pancreatic polypeptide, and somatostatin) to insulin-induced hypoglycemia were investigated in 18 insulin-dependent diabetics without residual beta-cell function and in 6 normal subjects. Nine of the diabetics had autonomic neuropathy, and 9 had no neuropathy. After hypoglycemia, no significant increase in any of the 3 pancreatic hormones was found in the diabetics with autonomic neuropathy, whereas significant increments were found in the diabetics without neuropathy and in the normal subjects. These results suggest that autonomic nervous activity is of major importance for pancreatic hormone release during hypoglycemia in man.

Paradoxically enhanced glucose production during exercise in humans with blocked glycolysis caused by muscle phosphofructokinase deficiency.

Muscle phosphofructokinase deficiency (PFKD) is characterized by exercise intolerance due to the enzymatic block in muscle glycolysis. Glucose infusion increases exertional fatigue in these patients, probably by decreasing the availability of free fatty acids (FFA) and ketones, which play a crucial role in ATP production during exercise in PFKD. This suggests that a lower than normal hepatic glucose production would be appropriate during exercise in PFKD. To investigate glucoregulation in PFKD, we measured glucose turnover and hormonal and metabolic responses to 20 minutes of cycle exercise at near maximal effort in three patients with PFKD and in healthy matched controls studied at the same absolute (A, 15 to 30 Watts) and relative (R, 35 to 80 Watts, matched heart rates) work load as the patients. During exercise, mean glucose production was higher in all patients versus controls (30 +/- 4 versus A: 18 +/- 2 and R: 20 +/- 1 mumol.min-1.kg-1). Mean glucose utilization during exercise was similar in patients and controls working at the same relative work load and higher than in controls at the low work load. Exercise-induced increases in arterialized blood were higher in all patients for glucose, FFA, growth hormone, glucagon, and norepinephrine. Plasma alanine and lactate always decreased during exercise in patients and consistently increased in controls. In conclusion, an enhanced neuroendocrine response and a paradoxically exaggerated mobilization of glucose occurs during exercise in PFKD. The responses are probably initiated by neural feedback elicited by disturbances in local muscle metabolism. The responses promote delivery of oxidizable fat to muscle, but at the expense of accumulation and futile cycling of glucose.

Fatigue and cardiac and endocrine metabolic response to exercise after abdominal surgery.

Subjective feeling of fatigue was quantified before and 20 days after elective uncomplicated abdominal surgery in 16 otherwise-healthy patients and compared with changes in heart rate and various hormonal and substrate responses to a 10-minute bicycle exercise (65% of preoperative maximal work capacity) preoperatively and postoperatively. Postoperatively, fatigue increased (p less than 0.001) from 3.0 +/- 0.5 to 5.3 +/- 0.5 arbitrary units (mean +/- SEM). Heart rate, plasma catecholamines, and serum growth hormone, lactate, alanine, and glycerol values always increased, whereas serum insulin values decreased in response to exercise (p less than 0.01). During exercise, only heart rate (p less than 0.01) and lactate (p less than 0.05) values were higher postoperatively compared with preoperatively. Increase in fatigue postoperatively correlated significantly to increase in heart rate (p less than 0.01) and correlated positively, but not significantly, to increase in plasma levels of noradrenaline (p = 0.08), growth hormone (p = 0.09), and alanine (p = 0.08) during exercise, but not to increase in serum lactate values (p greater than 0.8). Thus, after uncomplicated surgery, there was increased fatigue and amplified metabolic and cardiovascular response to a given absolute work load. These findings are similar to those observed during detraining and suggest a therapeutic role of exercise in the treatment of postoperative fatigue.

Training-induced enhancement of insulin action in human skeletal muscle: the influence of aging.

Age-induced reduction of whole body insulin action has been attributed to decreased insulin action in skeletal muscle. Physical training improves insulin action, but the effect has never been investigated specifically in aged human skeletal muscle. Seven young men [age: 23 +/- 1 yr (mean +/- SE; range, 21-24 yr); weight: 70 +/- 1 kg; body fat: 8 +/- 1%] and eight aged men [59 +/- 1 yr (range, 58-64 yr); 83 +/- 2 kg; 20 +/- 2%] performed one-legged bicycle training on a modified ergometer cycle for 10 weeks, 6 days/week, at 70% of VO2 peak. Glucose clearance rates in whole body and leg were measured 16 hr after training by a hyperinsulinemic (28, 88, and 480 mU.min-1.min-2), isoglycemic clamp combined with leg balance technique. Peak oxygen uptake during the bicycle test was always lower (p < .05) in aged vs. young subjects. Furthermore, VO2 peak was higher after training in trained (T) vs. untrained (UT) (p < .05) legs. Whole body glucose clearance rate was lower in aged vs. young subjects (p < .05) when expressed per kg body weight, but similar when expressed relative to fat free mass. Leg blood flow was always lower in aged vs. young men (p < .05). At basal and during insulin infusion, leg blood flow in young men did not differ significantly in T vs. UT legs (maximum insulin: 81 +/- 7 vs. 71 +/- 5 ml.min-1.kg leg-1), while in aged subjects it increased (p < .05) with training (maximum insulin: 57 +/- 5 vs. 48 +/- 5 ml.min-1.kg leg-1). Leg glucose extraction was always higher in aged vs. young men during the two last clamp steps (p < .05). Furthermore, leg glucose extraction was increased by training in young (p < .05) but not significantly in aged subjects. Leg glucose clearance rates increased (p < .05) with training and was similar in aged men (T: 1 +/- 1, 8 +/- 1, 21 +/- 2, and 24 +/- 2; UT: 1 +/- 1, 6 +/- 1, 14 +/- 2, and 20 +/- 2 ml.min-1.kg leg-1) and young men (T: 1 +/- 1, 12 +/- 3, 23 +/- 3, and 26 +/- 3; UT: 1 +/- 1, 8 +/- 2, 17 +/- 2, and 21 +/- 2 ml.min-1.kg leg-1). Therefore, insulin action in muscle is not reduced by aging. At high insulin concentrations, the leg blood flow is lower, whereas glucose extraction is higher in aged compared with young men. Training increases overall insulin action on glucose clearance in skeletal muscle identically in aged and young subjects.