Effects of insulin and exercise on rat hindlimb muscles after simulated microgravity.

This study was designed to examine insulin- and exercise-stimulated glucose uptake and metabolism in the hindlimb muscles of rats after conditions of simulated microgravity. To simulate microgravity, male Sprague-Dawley rats were suspended in a head-down (45 degrees) position with their hindlimbs non-weight bearing (SUS) for 14 days. In addition, rats were assigned to suspension followed by exercise (SUS-E), to cage control (CC), or to exercising control (CC-E) groups. Exercise consisted of five 10-min bouts of treadmill running at the same relative intensity for the CC-E and SUS-E rats (80-90% of maximum O2 consumption). Hindlimb perfusion results indicated that glucose uptake for the entire hindquarter at 24,000 microU/ml insulin (maximum stimulation) was significantly higher in the SUS (8.9 +/- 0.5 mumol.g-1.h-1) than in the CC (7.6 +/- 0.4 mumol.g-1.h-1) rats, signifying an increased insulin responsiveness. Glucose uptake at 90 microU/ml insulin was also significantly higher in the SUS (48 +/- 4; % of maximum stimulation over basal) than in the CC (21 +/- 4%) rats. In addition, exercise-induced increases in glucose uptake for the hindlimbs (133%) and glucose incorporation into glycogen for the plantaris (8.4-fold), extensor digitorum longus (5.4-fold), and white gastrocnemius (4.8-fold) muscles were greater for the SUS-E rats than for the CC-E rats (39% and 1.9-, 1.9-, and 3.0-fold, respectively). Therefore, suspension of the rat with hindlimbs non-weight bearing leads to enhanced muscle responses to insulin and exercise when they were applied separately. However, insulin action appeared to be impaired after exercise for the SUS-E rats, especially for the soleus muscle.     

Glucose metabolism in perfused skeletal muscle. Demonstration of insulin resistance in the obese Zucker rat.

1. The effect of insulin (0.5, 10 and 50 munits/ml of perfusate) on glucose uptake and disposal in skeletal muscle was studied in the isolated perfused hindquarter of obese (fa/fa) and lean (Fa/Fa) Zucker rats and Osborne-Mendel rats. 2. A concentration of 0.5 munit of insulin/ml induced a significant increase in glucose uptake (approx. 2.5 mumol/min per 30 g of muscle) in lean Zucker rats and in Osborne-Mendel rats, and 10 munits of insulin/ml caused a further increase to approx. 6 mumol/min per 30 g of muscle; but 50 munits of insulin/ml had no additional stimulatory effect. In contrast, in obese Zucker rats only 10 and 50 munits of insulin/ml had a stimulatory effect on glucose uptake, the magnitude of which was decreased by 50-70% when compared with either lean control group. Since under no experimental condition tested was an accumulation of free glucose in muscle-cell water observed, the data suggest an impairment of insulin-stimulated glucose transport across the muscle-cell membrane in obese Zucker rats. 3. The intracellular disposal of glucose in skeletal muscle of obese Zucker rats was also insulin-insensitive: even at insulin concentrations that clearly stimulated glucose uptake, no effect of insulin on lactate oxidation (nor an inhibitory effect on alanine release) was observed; [14C]glucose incorporation into skeletal-muscle lipids was stimulated by 50 munits of insulin/ml, but the rate was still only 10% of that observed in lean Zucker rats. 4. The data indicate that the skeletal muscle of obese Zucker rats is insulin-resistant with respect to both glucose-transport mechanisms and intracellular pathways of glucose metabolism, such as lactate oxidation. The excessive degree of insulin-insensitivity in skeletal muscle of obese Zucker rats may represent a causal factor in the development of the glucose intolerance in this species.     

Simulated first-phase insulin release using Humulin or insulin analog HIM2 is associated with prolonged improvement in postprandial glycemia

We examined the extent to which priming the liver with a pulse of Humulin or the insulin analog hexyl-insulin monoconjugate 2 (HIM2) reduces postprandial hyperglycemia. Somatostatin (0.5 microg.kg(-1).min(-1)) was given with basal intraportal insulin and glucagon for 4.5 h into three groups of 42-h-fasted conscious dogs. From 0-5 min, group 1 (BI, n = 6) received saline, group 2 (HI, n = 6) received a Humulin pulse (10 mU.kg(-1).min(-1)), and group 3 (HIM2, n = 6) received a HIM2 pulse (10 mU.kg(-1).min(-1)). Duodenal glucose was infused (5.0 mg.kg(-1).min(-1)) from 15 to 270 min. Arterial insulin in BI remained basal (6 +/- 1 microU/ml) and peaked at 52 +/- 15 (HI) and 164 +/- 44 microU/ml (HIM2) and returned to baseline by 30 and 60 min, respectively. Arterial plasma glucose plateaued at 265 +/- 20, 214 +/- 15, and 193 +/- 14 mg/dl in BI, HI, and HIM2. Glucose absorption was similar in all groups. Significant net hepatic glucose uptake occurred at 85, 55, and 25 min in BI, HI, and HIM2, respectively. Nonhepatic glucose clearance at 270 min differed among groups (BI, HI, HIM2): 0.62 +/- 0.11, 0.76 +/- 0.26, and 1.61 +/- 0.29 ml.kg(-1).min(-1) (P < 0.05). A brief (5-min) insulin pulse improved postprandial glycemia, stimulating hepatic glucose uptake and prolonging enhancement of nonhepatic glucose clearance. HIM2 was more effective than Humulin, perhaps because its lowered clearance caused higher levels at the liver and periphery and its biological activity was not reduced proportionally to its decreased clearance.     

Reversibility of decreased insulin-stimulated glucose transport capacity in diabetic muscle with in vitro incubation. Insulin is not required

The mechanisms by which insulin deficiency affects muscle glucose transport were investigated. Epitrochlearis muscles from rats with streptozotocin-induced diabetes and from controls were incubated in vitro for 0.5-14 h. The incubation was shown not to impair muscle energy stores or tissue oxygenation. Diabetes decreased basal 3-O-methylglucose transport by 40% (p less than 0.01), and insulin-stimulated (20 milli-units/ml) glucose transport capacity by 70% (p less than 0.001). In vitro incubation gradually normalized insulin responsiveness (3.77 +/- 0.38 before versus 8.97 +/- 0.65 mumol X ml-1 X h-1 after 12 h of incubation). Basal glucose transport remained significantly reduced. The reversal of the insulin responsiveness did not require the presence of rat serum and, furthermore, took place even in the absence of insulin. In fact, insulin responsiveness was higher after incubation (14 h) with no insulin than with 100 microunits/ml insulin (9.85 +/- 0.59 versus 8.06 +/- 0.59 mumol X ml-1 X h-1, p less than 0.05). Glucose at 30 mM did not affect the normalization of the insulin-stimulated glucose transport capacity, whereas incubation in serum from diabetic rats resulted in a slightly (26%) blunted reversal (7.60 +/- 0.39 versus 8.89 +/- 0.45 mumol X ml-1 X h-1 with diabetic versus control serum for 14 h, p less than 0.05; before incubation the value was 3.87 +/- 0.40). Inhibition of protein synthesis by cycloheximide blocked the normalization by 80%. These results suggest the presence in diabetic serum of some labile factor that might inhibit the glucose transport system. The results indicate that the decreased insulin-stimulated glucose transport capacity, in the insulin-deficient diabetic muscle, is not a direct consequence of the lack of insulin or of high glucose concentrations.     

Effects of exercise on insulin-induced hypoglycemia

The purpose of this study was to determine the effect of exercise on the rate of onset of hypoglycemia induced by infusion of excess insulin (0.8 mU.min-1.100 g-1). Rats were either fasted overnight (FS) or fed ad libitum (FD). FS rats were killed after 5, 10, or 15 min of infusion at rest or after running on the treadmill at 21 m/min and 15% grade. FD rats were killed after 10, 20, or 40 min of infusion at rest or after exercise. Rats were also killed 15 min postexercise for FS and 60 or 120 min postexercise for FD with continued insulin infusion. The progressive decline in blood glucose was not altered by exercise in the FS rats. FD rats showed a significant difference due to exercise only after 40 min (rest 4.2 +/- 0.3 mM, exercise 3.2 +/- 0.2 mM). A significant postexercise repletion of glycogen was observed in red vastus and soleus muscles of FD rats despite the decreasing blood glucose values. These data indicate that exercise accelerates the rate of development of hypoglycemia in FD rats. In the FS rats, where the rate of decline in blood glucose was greater, exercise had no effect on the time course of development of hypoglycemia.     

Gluconeogenesis predominates in periportal regions of the liver lobule

Rates of gluconeogenesis from lactate were calculated in periportal and pericentral regions of the liver lobule in perfused rat livers from increases in O2 uptake due to lactate. When lactate (0.1-2.0 mM) was infused into livers from fasted rats perfused in either anterograde or the retrograde direction, a good correlation (r = 0.97) between rates of glucose production and extra O2 uptake by the liver was observed as expected. Rates of oxygen uptake were determined subsequently in periportal and pericentral regions of the liver lobule by placing miniature oxygen electrodes on the liver surface and measuring the local change in oxygen concentration when the flow was stopped. Basal rates of oxygen uptake of 142 +/- 11 and 60 +/- 4 mumol X g-1 X h-1 were calculated for periportal and pericentral regions, respectively. Infusion of 2 mM lactate increased oxygen uptake by 71 mumol X g-1 X h-1 in periportal regions and by 29 mumol X g-1 X h-1 in pericentral areas of the liver lobule. Since the stoichiometry between glucose production and extra oxygen uptake is well-established, rates of glucose production in periportal and pericentral regions of the liver lobule were calculated from local changes in rates of oxygen uptake for the first time. Maximal rates of glucose production from lactate (2 mM) were 60 +/- 7 and 25 +/- 4 mumol X g-1 X h-1 in periportal and pericentral zones of the liver lobule, respectively. The lactate concentrations required for half-maximal glucose synthesis were similar (0.4-0.5 mM) in both regions of the liver lobule in the presence or absence of epinephrine (0.1 microM). In the presence of epinephrine, maximal rates of glucose production from lactate were 79 +/- 5 and 59 +/- 3 mumol X g-1 X h-1 in periportal and pericentral regions, respectively. Thus, gluconeogenesis from lactate predominates in periportal areas of the liver lobule during perfusion in the anterograde direction; however, the stimulation by added epinephrine was greatest in pericentral areas. Differences in local rates of glucose synthesis may be due to ATP availability, as a good correlation between basal rates of O2 uptake and rates of gluconeogenesis were observed in both regions of the liver lobule in the presence and absence of epinephrine. In marked contrast, when livers were perfused in the retrograde direction, glucose production was 28 +/- 5 mumol X g-1 X h-1 in periportal areas and 74 +/- 6 mumol X g-1 X h-1 in pericentral regions.(ABSTRACT TRUNCATED AT 400 WORDS)     

Insulin-induced hypoglycemia in fed and fasted exercising rats.

To determine running performance and hormonal and metabolic responses during insulin-induced hypoglycemia, fed and fasted male rats (315 +/- 3 g) were infused with insulin (100 mU/ml, 1.5 ml/h) or saline (1.5 ml/h) for 60 min and then killed at rest or after running on the treadmill (21 m/min, 15% grade). Insulin-infused fed rats ran poorly during the second 10 min of a 20-min exercise test. They were capable of running a total of 43 +/- 5 min, compared with 138 +/- 6 min for saline-infused fed rats. Fasted insulin-infused rats were able to run only 12.8 +/- 0.8 min, compared with 122 +/- 15 min for fasted saline-infused rats. In fasted rats, blood glucose was 1.6 +/- 0.1 mM after 60 min of insulin infusion and 1.2 +/- 0.1 mM after running to exhaustion. Artificial increase of plasma free fatty acids had no effect on performance. Intravenous infusion of glucose at the time of fatigue produced an immediate recovery, allowing the formerly fatigued rats to run 20 min without development of fatigue. These results provide evidence that severe hypoglycemia can be a significant cause of fatigue, even if it occurs early in the course of an exercise bout.     

Sensory nerve inactivation by resiniferatoxin improves insulin sensitivity in male obese Zucker rats

Recent studies have suggested that sensory nerves may influence insulin secretion and action. The present study investigated the effects of resiniferatoxin (RTX) inactivation of sensory nerves (desensitization) on oral glucose tolerance, insulin secretion and whole body insulin sensitivity in the glucose intolerant, hyperinsulinemic, and insulin-resistant obese Zucker rat. After RTX treatment (0.05 mg/kg RTX sc given at ages 8, 10, and 12 wk), fasting plasma insulin was reduced (P < 0.0005), and oral glucose tolerance was improved (P < 0.005). Pancreas perfusion showed that baseline insulin secretion (7 mM glucose) was lower in RTX-treated rats (P = 0.01). Insulin secretory responsiveness to 20 mM glucose was enhanced in the perfused pancreas of RTX-treated rats (P < 0.005) but unaffected in stimulated, isolated pancreatic islets. At the peak of spontaneous insulin resistance in the obese Zucker rat, insulin sensitivity was substantially improved after RTX treatment, as evidenced by higher glucose infusion rates (GIR) required to maintain euglycemia during a hyperinsulinemic euglycemic (5 mU.kg(-1).min(-1)) clamp (GIR(60-120min): 5.97 +/- 0.62 vs. 11.65 +/- 0.83 mg.kg(-1).min(-1) in RTX-treated rats, P = 0.003). In conclusion, RTX treatment and, hence, sensory nerve desensitization of adult male obese Zucker rats improved oral glucose tolerance by enhancing insulin secretion, and, in particular, by improving insulin sensitivity.     

Duration of Improved Muscle Glucose Uptake After Acute Exercise in Obese Zucker Rats

Skeletal muscle is insulin resistant in the obese Zucker rat. Endurance training reduces muscle insulin resistance, but the effects of a single acute exercise session on muscle insulin resistance in the obese Zucker rat are unknown. Therefore, insulin responsiveness of muscle glucose uptake was measured in 15-week-old obese rats either 1, 48, or 72 hours after two hours of intermittent exercise (3030 min; work:rest). Hindlimbs of sedentary lean (LS) and obese (OS) rats and exercised obese (OE) rats were perfused after a 10-hour fast under both basal (0 mU.ml^?1) and maximal (20 mU.ml^?1) insulin concentrations to measure net glucose uptake. Insulin responsiveness of net glucose uptake was significantly reduced in OS compared to LS (8.5 ± 1.6 vs 15.3 ± 2.0 μmol.g^?1.h^?1, respectively). Compared to OS, insulin responsiveness of net glucose uptake was significantly increased by 56% and 80% at 1 hour and 48 hours after acute exercise. However, 72 hours after acute exercise, the increased insulin responsiveness of net glucose uptake was no longer evident. These results indicate that improved responsiveness of muscle glucose uptake persists for at least 48 hours after two hours of acute intermittent exercise in 15-week-old obese Zucker rats. (OBESITY RESEARCH 1993; 1:295–302)     

Muscle glucose transport: interactions of in vitro contractions, insulin, and exercise

Exercise increases permeability of muscle to glucose. Normally, the effects of exercise and a maximal insulin stimulus on glucose transport are additive. However, the combined effect on rat epitrochlearis muscle permeability to 3-O-methylglucose (3-MG) of a maximal insulin stimulus followed by in vitro contractile activity of 1.24 +/- 0.06 mumol.10 min-1.ml intracellular water-1 was no greater than that of either stimulus alone. We found that this absence of an additive effect was caused by prolonged exposure to an unphysiologically high insulin concentration (20,000 microU/ml for 60 min), which, in addition to stimulating glucose transport, appears to prevent further increases in permeability to glucose. When the treatments were reversed and muscles were first stimulated to contract and then incubated with 20,000 microU/ml insulin, 3-MG uptake (mumol.10 min-1.ml intracellular water-1) increased from a control value of 0.26 +/- 0.03 to 1.80 +/- 0.15, compared with 1.04 +/- 0.06 for contractile activity alone, 1.21 +/- 0.08 for insulin, and 1.88 +/- 0.11 for exercise (swimming) plus insulin. Swimming plus in vitro contractile activity did not have a greater effect than contractile activity alone. Our results provide evidence that 1) the effect of exercise on muscle permeability to glucose is mediated solely by a process associated with contractile activity, and 2) it is advisable to avoid the use of unphysiologically high insulin concentrations in studies designed to elucidate in vivo actions of insulin.     

Skeletal muscle glucose transport in obese Zucker rats after exercise training

Exercise training has been found to reduce the muscle insulin resistance of the obese Zucker rat (fa/fa). The purpose of the present study was to determine whether this reduction in muscle insulin resistance was associated with an improvement in the glucose transport process and if it was fiber-type specific. Rats were randomly assigned to a sedentary or training group. Training consisted of treadmill running at 18 m/min up an 8% grade, 1.5 h/day, 5 days/wk, for 6-8 wk. The rate of muscle glucose transport was assessed in the absence of insulin and in the presence of a physiological (0.15 mU/ml), a submaximal (1.50 mU/ml), and a maximal (15.0 mU/ml) insulin concentration by determining the rate of 3-O-methyl-D-glucose (3-OMG) accumulation during hindlimb perfusion. The average 3-OMG transport rate of the red gastrocnemii (fast-twitch oxidative-glycolytic fibers) was significantly higher in the trained compared with the sedentary obese rats in the absence of insulin and in the presence of the three insulin concentrations. Significant improvements in 3-OMG transport were also observed in the plantarii (mixed fibers) of trained obese rats in the presence of 0, 0.15, and 15.0 mU/ml insulin. Training appeared to have little effect on the insulin-stimulated 3-OMG transport of the soleus (slow-twitch oxidative fibers) or white gastrocnemius (fast-twitch glycolytic fibers). The results suggest that the improvement in the muscle insulin resistance of the obese Zucker rat after moderate endurance training was associated with an improvement in the glucose transport process but that it was fiber-type specific.     

Muscle glycogen storage after different amounts of carbohydrate ingestion

The purpose of this study was to determine whether the rate of muscle glycogen storage could be enhanced during the initial 4-h period postexercise by substantially increasing the amount of the carbohydrate consumed. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. Immediately and 2 h after exercise they consumed either 0 (P), 1.5 (L), or 3.0 g glucose/kg body wt (H) from a 50% glucose polymer solution. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately, 2 h, and 4 h after exercise. Blood glucose and insulin declined significantly during exercise in each of the three treatments. They remained below the preexercise concentrations during recovery in the P treatment but increased significantly above the preexercise concentrations during the L and H treatments. By the end of the 4 h-recovery period, blood glucose and insulin were still significantly above the preexercise concentrations in both treatments. Muscle glycogen storage was significantly increased above the basal rate (P, 0.5 mumol.g wet wt-1.h-1) after ingestion of either glucose polymer supplement. The rates of muscle glycogen storage, however, were not different between the L and H treatments during the first 2 h (L, 5.2 +/- 0.9 vs. H, 5.8 +/- 0.7 mumol.g wet wt-1.h-1) or the second 2 h of recovery (L, 4.0 +/- 0.9 vs. H, 4.5 +/- 0.6 mumol.g wet wt-1. h-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.

Exercise training improves skeletal muscle insulin sensitivity in the obese Zucker rat. The purpose of this study was to investigate whether the improvement in insulin action in response to exercise training is associated with enhanced insulin receptor signaling. Obese Zucker rats were trained for 7 wk and studied by using the hindlimb-perfusion technique 24 h, 96 h, or 7 days after their last exercise training bout. Insulin-stimulated glucose uptake (traced with 2-deoxyglucose) was significantly reduced in untrained obese Zucker rats compared with lean controls (2.2 +/- 0.17 vs. 5.4 +/- 0.46 micromol x g(-1) x h(-1)). Glucose uptake was normalized 24 h after the last exercise bout (4.9 +/- 0.41 micromol x g(-1) x h(-1)) and remained significantly elevated above the untrained obese Zucker rats for 7 days. However, exercise training did not increase insulin receptor or insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3-kinase) activity associated with IRS-1 or tyrosine phosphorylated immunoprecipitates, or Akt serine phosphorylation. These results are consistent with the hypothesis that, in obese Zucker rats, adaptations occur during training that lead to improved insulin-stimulated muscle glucose uptake without affecting insulin receptor signaling through the PI3-kinase pathway.     

Three months energy restricted diet does not reduce peripheral insulin resistance in newly diagnosed non insulin dependent diabetics

Sixteen newly diagnosed non insulin dependent diabetic patients were treated for 3 months with an individual energy restricted diet. The effect on weight, hyperglycaemia and insulin response to oral glucose was measured in all subjects, and in 7, peripheral insulin resistance was estimated using a hyperinsulinaemic glucose clamp at two insulin infusion rates (40 and 400 mU m-2 X min-1). After diet, fasting plasma glucose fell from 12.0 +/- 0.7 mmol/l (mean +/- SEM) to 7.4 +/- 0.5 mmol/l (P less than 0.001) and weight fell from 92.9 +/- 4.2 kg to 85.0 +/- 3.1 kg (P less than 0.001). The plasma insulin response to oral glucose was unchanged after diet therapy. Insulin induced glucose disposal (M) was also unaffected by diet at insulin infusion rates of 40 mU m-2 X min-1 (12.5 +/- 1.5 mumol X kg-1 X min-1 vs 15.7 +/- 1.6 mumol X kg-1 X min-1) and 400 mU m-2 X min-1 (49.5 +/- 2.7 mumol X kg-1 X min-1 vs 55.1 +/- 2.5 mumol X kg-1 X min-1). These results show that 3 months reduction of energy consumption with weight loss in newly diagnosed non insulin dependent diabetics improves B-cell responsiveness to glucose but has no effect on liver glucose output or on peripheral insulin action.     

Venous versus arterialised venous blood for assessment of blood glucose levels during glucose clamping: comparison in healthy men.

The aim of this study was to investigate the influence of the arteriovenous (A-V) gradient in blood glucose concentrations at low and high insulin levels on the determination of glucose requirements during glucose clamping in 9 healthy, insulin sensitive, male volunteers. In a random order two clamps were performed, once using arterialised venous blood (A Clamp, mean pO2 = 11.5 +/- 0.36 kPa, 86 +/- 2.7 mmHg), and once using venous blood (V clamp, mean pO2 = 7.9 +/- 0.21 kPa, 59 +/- 1.6 mmHg). Insulin levels were maintained at 48 +/- 2.4 mU/l from 0-180 min and at 1054 +/- 114 mU/l from 180-360 min. Elevation of insulin levels caused a significant rise of the A-V gradient: from 0.3 +/- 0.1 to 0.5 +/- 0.1 mmol/l (p < 0.05) and from 0.2 +/- 0.1 to 0.3 +/- 0.1 mmol/l (p < 0.05) during the A and V clamps, respectively. Despite these A-V glucose gradients no significant differences were found for the glucose requirements during the last 30 min of each period of insulin infusion between the A and V clamps: 43.70 +/- 3.4 vs 44.8 +/- 2.8 mumol.kg-1.min-1 during the low insulin level and 77.3 +/- 5.0 vs 76.2 +/- 3.4 mumol.kg-1.min-1 during the high insulin level. We conclude that the A-V glucose gradient, even at high insulin levels, does not influence the assessment of glucose requirements to a measurable extent, allowing the use of the simpler technique of taking venous rather than arterialised venous blood for the measurements of glucose levels during glucose clamping.     

Eccentric exercise induces transient insulin resistance in healthy individuals.

Euglycemic-hyperinsulinemic clamps were performed on six healthy untrained individuals to determine whether exercise that induces muscle damage also results in insulin resistance. Clamps were performed 48 h after bouts of predominantly 1) eccentric exercise [30 min, downhill running, -17% grade, 60 +/- 2% maximal O2 consumption (VO2max)], 2) concentric exercise (30 min, cycle ergometry, 60 +/- 2% VO2max), or 3) without prior exercise. During the clamps, euglycemia was maintained at 90 mg/dl while insulin was infused at 30 mU.m-2.min-1 for 120 min. Hepatic glucose output (HGO) was determined using [6,6-2H]glucose. Eccentric exercise caused marked muscle soreness and significantly elevated creatine kinase levels (273 +/- 73, 92 +/- 27, 87 +/- 25 IU/l for the eccentric, concentric, and control conditions, respectively) 48 h after exercise. Insulin-mediated glucose disposal rate was significantly impaired (P less than 0.05) during the clamp performed after eccentric exercise (3.47 +/- 0.51 mg.kg-1.min-1) compared with the clamps performed after concentric exercise (5.55 +/- 0.94 mg.kg-1.min-1) or control conditions (5.48 +/- 1.0 mg.kg-1.min-1). HGO was not significantly different among conditions (0.77 +/- 0.26, 0.65 +/- 0.27, and 0.66 +/- 0.64 mg.kg-1.min-1 for the eccentric, concentric, and control clamps, respectively). The insulin resistance observed after eccentric exercise could not be attributed to altered plasma cortisol, glucagon, or catecholamine concentrations. Likewise, no differences were observed in serum free fatty acids, glycerol, lactate, beta-hydroxybutyrate, or alanine. These results show that exercise that results in muscle damage, as reflected in muscle soreness and enzyme leakage, is followed by a period of insulin resistance.     

Exercise training intensity/volume affects plasma and tissue adiponectin concentrations in the male rat

The objective of the study was to determine the effects of exercise training intensity/volume on plasma total and high molecular weight (HMW) adiponectin and tissue total adiponectin concentrations. Thirty-two, eight week-old male Wistar rats (185 ± 5 g) were randomly assigned to one of four groups: high intensity (HI: 34 m/min ∼%80-%85 VO₂max), moderate intensity (MI: 28 m/min ∼%70-%75 VO₂max), low intensity (LI: 20m/min ∼ %50-%55 VO₂max), and sedentary control (SED). Experimental groups completed a 12-week exercise program of treadmill running at 0° slope, 1 h/day, 5 days/week. Since frequency and duration of exercise were identical among training groups, the volume of training was highest in the HI group followed by the MI and LI groups. Compared with SED animals, fasting plasma total and HMW adiponectin and adipose tissue total adiponectin concentrations were significantly higher in the HI and MI groups, but total adiponectin concentrations in liver and soleus muscle were not significantly lower than the SED rats. There were significantly lower plasma total testosterone levels in the HI group vs. SED group. Plasma total and HMW adiponectin were negatively correlated with HOMA-IR and insulin whereas total adiponectin was inversely related to TNF-α and HMW adiponectin was negatively correlated with total testosterone. Thus, data suggest there is a dose effect for exercise training intensity and accompanying volume for the adaptation of adipose tissue and circulating total and HMW adiponectin concentrations, whereas the changes of adiponectin concentrations in skeletal muscle and liver tissue may depend on the body's energy balance in the recovery period.     

Lactate, fructose and glucose oxidation profiles in sports drinks and the effect on exercise performance

Exogenous carbohydrate oxidation was assessed in 6 male Category 1 and 2 cyclists who consumed CytoMax (C) or a leading sports drink (G) before and during continuous exercise (CE). C contained lactate-polymer, fructose, glucose and glucose polymer, while G contained fructose and glucose. Peak power output and VO2 on a cycle ergometer were 408+/-13 W and 67.4+/-3.2 mlO2 x kg(-1) x min(-1). Subjects performed 3 bouts of CE with C, and 2 with G at 62% VO2peak for 90 min, followed by high intensity (HI) exercise (86% VO(2)peak) to volitional fatigue. Subjects consumed 250 ml fluid immediately before (-2 min) and every 15 min of cycling. Drinks at -2 and 45 min contained 100 mg of [U-(13)C]-lactate, -glucose or -fructose. Blood, pulmonary gas samples and 13CO2 excretion were taken prior to fluid ingestion and at 5,10,15,30,45,60,75, and 90 min of CE, at the end of HI, and 15 min of recovery. HI after CE was 25% longer with C than G (6.5+/-0.8 vs. 5.2+/-1.0 min, P<0.05). 13CO2 from the -2 min lactate tracer was significantly elevated above rest at 5 min of exercise, and peaked at 15 min. 13CO2 from the -2 min glucose tracer peaked at 45 min for C and G. 13CO2 increased rapidly from the 45 min lactate dose, and by 60 min of exercise was 33% greater than glucose in C or G, and 36% greater than fructose in G. 13CO2 production following tracer fructose ingestion was greater than glucose in the first 45 minutes in C and G. Cumulative recoveries of tracer during exercise were: 92%+/-5.3% for lactate in C and 25+/-4.0% for glucose in C or G. Recoveries for fructose in C and G were 75+/-5.9% and 26+/-6.6%, respectively. Lactate was used more rapidly and to a greater extent than fructose or glucose. CytoMax significantly enhanced HI.     

Effect of training intensity on insulin sensitivity as evaluated by insulin tolerance test

The purpose of this study was to evaluate the role of exercise intensity in the effect of physical training on insulin sensitivity. The insulin tolerance test (ITT) was applied to quantify insulin sensitivity. Eighteen healthy, young, untrained men and women participated in a 4-week, five times per week, 1-h per session bicycle-ergometer training program. Training consisted of 3-min bouts of cycling interspersed with 2 min at a lower exercise intensity. Intensities were 80 and 40% of pretraining maximal power output (W(max)) in the high-intensity (HI) and 40 and 20% W(max) in the low-intensity (LI) group. The insulin sensitivity index (IS(index)) was similar in the HI and LI group before the training intervention [mean (SD) -0.1898 (0.058) and -0.1892 (0.045), respectively]. After training, the IS(index) was -0.2358 (0.051) (P = 0.005 vs pretraining) in the HI group and -0.2050 (0.035) (P = 0. 099 against pretraining) in the LI group. We conclude that improvements in insulin sensitivity are more pronounced with high-intensity training, when exercise frequency and duration are kept similar. We further conclude that the ITT is suitable for use in intervention studies.     

Urea synthesis from ammonia in periportal and pericentral regions of the liver lobule. Effect of oxygen

Rates of urea synthesis were determined in periportal and pericentral regions of the liver lobule in perfused liver from fed, phenobarbital-treated rats by measuring the extra O2 consumed upon infusion of NH4Cl with miniature O2 electrodes and from decreases in NADPH fluorescence detected with micro-light-guides. Urea synthesis by the perfused rat liver supplemented with lactate (5 mM), ornithine (2 mM) and methionine sulfoximine (0.15 mM), an inhibitor of glutamine synthetase, was stimulated by stepwise infusion of NH4Cl at doses ranging from 0.24 mM to 3.0 mM. A good correlation (r = 0.92) between decreases in NADPH fluorescence and urea production was observed when the NH4Cl concentration was increased. Sublobular rates of O2 uptake were determined by placing miniature oxygen electrodes on periportal or pericentral regions of the lobule on the liver surface, stopping the flow and measuring decreases in oxygen tension. From such measurements local rates of O2 uptake were calculated in the presence and absence of NH4Cl and local rates of urea synthesis were calculated from the extra O2 consumed in the presence of NH4Cl and the stoichiometry between O2 uptake and urea formation. Rates of urea synthesis were also estimated from the fractional decrease in NADPH fluorescence, caused by NH4Cl infusion in each region, measured with micro-light-guides and the rate of urea synthesis by the whole organ. When perfusion was in the anterograde direction, maximal rates of urea synthesis, calculated from changes in fluorescence, were 177 +/- 31 mumol g-1 h-1 and 61 +/- 24 mumol g-1 h-1 in periportal and pericentral regions, respectively. When perfusion was in the retrograde direction, however, rates were 76 +/- 23 mumol g-1 h-1 in periportal areas and 152 +/- 19 mumol g-1 h-1 in pericentral regions. During perfusion in the anterograde direction, urea synthesis, calculated by changes in O2 uptake, was 307 +/- 76 mumol g-1 h-1 and 72 +/- 34 mumol g-1 h-1 in periportal and pericentral regions, respectively. When perfusion was in the retrograde direction, urea was synthesized at rates of 54 +/- 17 mumol g-1 h-1 and 387 +/- 99 mumol g-1 h-1 in periportal and pericentral regions, respectively. Thus, maximal rates of urea synthesis were dependent upon the direction of perfusion. In addition, rates of urea synthesis were elevated dramatically in periportal regions when the flow rate per gram liver was increased (e.g. 307 versus 177 mumol g-1 h-1).(ABSTRACT TRUNCATED AT 400 WORDS)