Effect of exercise on food consumption and appetite sensations in subjects with diabetes.

AIM: Evaluate appetite sensations following 60-min moderate intensity exercise and to predict energy intake in adults with diabetes. METHODS: Visual analogue scales measured appetite sensations before and after a fixed test meal. Fasting appetite sensations, 1h post-prandial area under the curve (AUC) and the satiety quotient predicted energy intake. Two measures of energy intake were recorded: (1) following an ad libitum test lunch and (2) a 3-day self-report dietary record. Appetite sensations were assessed in a control condition (rest, C) and when two exercise sessions were performed: one associated with a free (F) blood glucose decrease and one with limited blood glucose decreases i.e. maintained (M) above 4 mmol/l by dextrose infusion. RESULTS: 16 generally well-controlled (HbA1c: 7.0 ± 0.6%) subjects (12 with type 1 diabetes, 4 with type 2 diabetes) ate 1020 ± 519, 1170 ± 282 and 1020 ± 304 kcal (NS between conditions nor diabetes type) during the buffet meal following the C, F and M conditions, respectively. Exercise induced a mean blood glucose decrease of 3.7 ± 0.6 and 3.1 ± 0.6 mmol/l for the F and M conditions, respectively. The greater the blood glucose decrease, the greater the appetite sensations of hunger and prospective food consumption measured fasting and before the test meal (all p<0.05) in the whole group. One-hour post-prandial AUC for hunger and desire to eat represented the strongest predictors of ad libitum test lunch energy intake (p<0.05), especially in type 1 diabetes. CONCLUSIONS: These results suggest that appetite sensations are predictors of spontaneous energy intake in both diabetes type. Moderate intensity exercise for 60 min induced a positive effect by lowering blood glucose which was associated with appetite sensations. These results support the glucostatic theory of food intake control which protects against exercised-induced blood glucose declines.

Dopaminergic neurodegeneration in a rat model of long-term hyperglycemia: preferential degeneration of the nigrostriatal motor pathway.

Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms. Considering the lack of literature addressing dopaminergic alterations in diabetes with age, the goal of this study was to characterize the state of 2 critical dopaminergic pathways in the nicotinamide-streptozotocin rat model of long-term hyperglycemia, specifically the nigrostriatal motor pathway and the reward-associated mesocorticolimbic pathway. Neuronal and glial alterations were evaluated 3 and 6 months after hyperglycemia induction, demonstrating preferential degeneration of the nigrostriatal pathway complemented by a noticeable astrogliosis and loss of microglial cells throughout aging. Behavioral tests confirmed the existence of motor impairments in hyperglycemic rats that resemble early parkinsonian symptomatology in rats, pensuing from nigrostriatal alterations. These results solidify the relation between hyperglycemia and nigrostriatal dopaminergic neurodegeneration, providing new insight on the higher occurrence of Parkinson's disease in diabetic patients.

Labeled CO(2) production and oxidative vs nonoxidative disposal of labeled carbohydrate administered at rest.

Carbon isotopes (*C) have been extensively used in man to describe oxidative vs nonoxidative disposal of an exogenous load of labeled carbohydrate (*C-CHO) at rest in various experimental situations. It is hypothesized that V*CO(2) reflects *C-CHO oxidation. However, when glycogen is synthesized through the indirect pathway (which is responsible for approximately 50% of glycogen storage), *C could be lost, diluted, and exchanged in the pyruvate-lactate pool, in the pool of tricarboxylic acid cycle intermediates, as well as at the entrance of the tricarboxylic acid cycle, and along the pathway of gluconeogenesis. This could result in a lower *C/C in the glycogen stored than in the CHO administered, in an increased production of *CO(2), and, respectively, in an overestimation and an underestimation of the oxidative and nonoxidative disposal of the CHO load. Results from the present experiment offer a support to this hypothesis. Over a 10-hour period after ingestion of a (13)C-pasta meal (313+/-10 g dry mass or 258+/-8 g of glucose) in 12 healthy subjects (6 men and 6 women), exogenous CHO oxidation computed from V(13)CO(2) (recovery factor, 0.54) significantly exceeded total CHO oxidation computed by indirect respiratory calorimetry corrected for urea excretion: 154.2+/-2.6 vs 133.5+/-3.2 g. In an additional study conducted in rats, (13)C/(12)C in glycogen stores was significantly approximately 50% lower than in the (13)C-CHO ingested, over a wide range of enrichment. These results suggest that because of dilution, loss, and exchange of *C in the indirect pathway of glycogen synthesis, the oxidative vs nonoxidative disposal of exogenous *C-CHO cannot be accurately tracked from V*CO(2).

Exercise and newer insulins: how much glucose supplement to avoid hypoglycemia?

PURPOSE: To determine the glucose supplement required to prevent hypoglycemia during moderate-intensity exercise in Type 1 diabetic patients using newer analog insulins. METHODS: Nine subjects performed 60 min of ergocycle exercise (50% VO2max), 3 h after a standard breakfast in three different conditions. Subjects were randomly assigned to preexercise liquid glucose supplement of 0 g of glucose (0G), 15 g of glucose (15G), and 30 g of glucose (30G). Blood glucose (BG) was measured before, during, and following the exercise. All subjects used Humulin N (N) and analog insulin Humalog (Lispro). A dextrose infusion was initiated when BG fell below 5 mmol x L(-1). RESULTS: There was no significant difference in the magnitude of the decrease in BG exercise-induced when comparing the three experimental conditions. However, the quantity of dextrose infused was significantly higher in the 0G (10.5 +/- 3.2 g) than in the 15G (3.5 +/- 1.8 g) or the 30G conditions (1.6 +/- 1.0 g). The addition of a glucose supplement (15G or 30G) significantly prolonged the delay before the need for dextrose infusion (31.7 +/- 7.5, 51.3 +/- 4.2, and 55.6 +/- 2.6 min; 0G, 15G, and 30G, respectively). The quantity of dextrose infusion was plotted against the three preexercise glucose supplements and a regression equation obtained. Solving this equation, a glucose supplement of 40 g was estimated in order to maintain BG levels within the normal range during and after exercise. CONCLUSION: For 60 min of late postprandial exercise followed by 60 min of recovery, an estimated 40 g of a liquid glucose supplement, ingested 15 min prior exercise, would seem likely to help maintain safe BG levels in subjects using N-Lispro.

Swim training increases glucose output from liver perfused in situ with glucagon in fed and fasted rats.

The effect of endurance swim training (3 hours per day, 5 days/week, for 10 weeks) on hepatic glucose production (HGP) in liver perfused in situ for 60 minutes with glucagon and insulin was studied in Sprague-Dawley rats. The experiments were performed in fed rats and in rats fasted for 24 hours, but with lactate (8 mmol/L) added to the perfusion medium. Liver glycogen content was significantly lower in fasted than fed rats (fasted untrained and trained: 14 +/- 4 and 11 +/- 3 micromol glycosyl U/g of liver wet weight (WW); fed untrained and trained: 205 +/- 11 and 231 +/- 11 micromol glycosyl U/g of liver WW; not significantly different in trained and untrained rats). Glucagon increased HGP in the 4 experimental groups, but the increases were more rapid and pronounced in trained than in untrained rats in both fed and fasted states. HGP values (area under the curve [AUC] in micromol/g of liver WW) were significantly higher in trained fed (112.1 +/- 7.1 v 85.9 +/- 12.2 in untrained rats) than in trained fasted rats (50.8 +/- 4.4 v 34.7 +/- 3.6 in untrained rats). When compared with untrained rats, the total amount of glucose released by the liver in response to glucagon in trained rats was approximately 30% higher in the fed state and approximately 45% larger in the fasted state. These results indicate that endurance training increases the response of both glycogenolysis and gluconeogenesis to glucagon.

Oral [(13)C]glucose and endogenous energy substrate oxidation during prolonged treadmill running.

Six male subjects were studied during running exercise (120 min, 69% maximal oxygen consumption) with ingestion of a placebo or 3.5 g/kg of [(13)C]glucose (approximately 2 g/min). Indirect respiratory calorimetry corrected for urea excretion in urine and sweat, production of (13)CO(2) at the mouth, and changes in plasma glucose (13)C/(12)C were used to compute energy substrate oxidation. The oxidation rate of exogenous glucose increased from 1.02 at minute 60 to 1.22 g/min at minute 120 providing approximately 24 and 33% of the energy yield (%En). Glucose ingestion did not modify protein oxidation, which provided approximately 4-5%En, but significantly increased glucose oxidation by approximately 7%, reduced lipid oxidation by approximately 16%, and markedly reduced endogenous glucose oxidation (1.25 vs. 2.21 g/min between minutes 80 and 120, respectively). The oxidation rate of glucose released from the liver (0.38 and 0.47 g/min, or 10-13%En at minutes 60 and 120, respectively), and of plasma glucose (1.30-1.69 g/min, or 34 and 45%En and 50 and 75% of glucose oxidation) significantly increased from minutes 60 to 120, whereas the oxidation of muscle glycogen significantly decreased (1.28 to 0.58 g of glucose/min, or 34 and 16%En and 50 and 25% of glucose oxidation). These results indicate that, during moderate prolonged running exercise, ingestion of a very large amount of glucose significantly reduces endogenous glucose oxidation, thus sparing muscle and/or liver glycogen stores.

Effects of carbohydrate availability on sustained shivering I. Oxidation of plasma glucose, muscle glycogen, and proteins.

Carbohydrates (CHO) can play an important thermogenic role during shivering, but the effect of their availability on the use of other oxidative fuels is unclear. Using indirect calorimetry and tracer methods ([U-13C]glucose ingestion), we have determined the specific contributions of plasma glucose, muscle glycogen, proteins, and lipids to total heat production (Hprod) in men exposed to cold for 2-h (liquid-conditioned suit perfused with 10 degrees C water). Measurements were made after low-CHO diet and exercise (Lo) and high-CHO diet without exercise (Hi). The size of CHO reserves had no effect on Hprod but a major impact on fuel selection before and during shivering. In the cold, a complete shift from lipid oxidation for Lo (53, 28, and 19% Hprod for lipids, CHO, and proteins, respectively) to CHO-based metabolism for Hi (23, 65, and 12% Hprod for lipids, CHO, and proteins, respectively) was observed. Plasma glucose oxidation remains a minor fuel under all conditions (<13% Hprod), falling to 7% Hprod for Lo. Therefore, adjusting plasma glucose oxidation to compensate for changes in muscle glycogen oxidation is not a strategy used for maintaining heat production. Instead, proteins and lipids share responsibility for this compensation. We conclude that humans can show remarkable flexibility in oxidative fuel selection to ensure that heat production is not compromised during sustained cold exposure.

Effect of cold exposure on fuel utilization in humans: plasma glucose, muscle glycogen, and lipids.

The relative roles of circulatory glucose, muscle glycogen, and lipids in shivering thermogenesis are unclear. Using a combination of indirect calorimetry and stable isotope methodology ([U-13C]glucose ingestion), we have quantified the oxidation rates of these substrates in men acutely exposed to cold for 2 h (liquid conditioned suit perfused with 10 degrees C water). Cold exposure stimulated heat production by 2.6-fold and increased the oxidation of plasma glucose from 39.4 +/- 2.4 to 93.9 +/- 5.5 mg/min (+138%), of muscle glycogen from 126.6 +/- 7.8 to 264.2 +/- 36.9 mg glucosyl units/min (+109%), and of lipids from 46.9 +/- 3.2 to 176.5 +/- 17.3 mg/min (+376%). Despite the observed increase in plasma glucose oxidation, this fuel only supplied 10% of the energy for heat generation. The major source of carbohydrate was muscle glycogen (75% of all glucose oxidized), and lipids produced as much heat as all other fuels combined. During prolonged, low-intensity shivering, we conclude that total heat production is unequally shared among lipids (50%), muscle glycogen (30%), plasma glucose (10%), and proteins (10%). Therefore, future research should focus on lipids and muscle glycogen that provide most of the energy for heat production.

Relation between energy intake and glycemic control in physically active young adults with type 1 diabetes.

OBJECTIVES: To examine the relationships between daily energy expenditure, energy intake and glycemic control in young adults with type 1 diabetes. DESIGN: Cross-sectional study. METHODS: Energy expenditure (kcal kg(-1)d(-1)) and duration of participation in physical activity were measured from a 3-d activity diary and categorized according to their intensity on a 1-9 scale. Energy intake was measured by a 3-d food record. Glycemic control was measured using the HbA1c. RESULTS: Energy expenditure and intake were assessed in 35 young adults with type 1 diabetes (age: 28 ± 7 years). Participants with higher energy expenditure from moderate to intense physical activity (categories 6-9) presented higher proportion of energy intake derived from carbohydrate and lower proportion of lipids in the diet with significantly higher HbA(1c) values (7.3 ± 1.0% vs 6.7 ± 0.6%). CONCLUSIONS: These results suggest that highly physically active individuals with type 1 diabetes consume more carbohydrates than lipids, a strategy that may affect their glycemic control. Further studies are needed to develop interventions to improve glycemic control in highly active individuals with type 1 diabetes.

Glucose or intermittent high-intensity exercise in glargine/glulisine users with T1DM.

INTRODUCTION: The effects of glargine/glulisine insulin regimen on exercise blood glucose (BG) and strategies to limit exercise-induced hypoglycemia are not well documented. Intermittent high-intensity exercise has been proposed to prevent hypoglycemia, but its effect in participants with type 1 diabetes using glargine/glulisine is unknown. METHODS: The study used a repeated-measures design with three randomly ordered exercise conditions. Eleven participants completed 60 min of moderate-intensity exercise at 50% VO(2peak) for all conditions. These conditions varied as follows: participants ingested 0 g of glucose preexercise (0G + MOD), 30 g of glucose preexercise (30G + MOD), or 0 g of glucose preexercise but performed brief high-intensity intervals interspersed every 2 min (0G + MOD/INT) during exercise. If BG fell <4 mmol·L(-1), a 20% dextrose solution was started to maintain BG between 4 and 5 mmol·L(-1). RESULTS: Consuming 30 g of glucose before exercise (30G + MOD) resulted in a higher preexercise BG (11.7 ± 2.7 mmol·L(-1)) compared with 0 g of glucose before exercise (0G + MOD, 7.8 ± 4.0, and 0G + MOD/INT, 9.2 ± 3.5mmol·L(-1)), P < 0.05. A dextrose infusion was required in 7/11, 4/11, and 1/11 participants for 0G + MOD, 0G + MOD/INT, 30G + MOD conditions, respectively, P < 0.02. The duration and the quantity of dextrose infused were greatest in the 0G + MOD condition, moderate in the to 0G + MOD/INT condition, and minimal in the 30G + MOD condition, P < 0.01. CONCLUSION: Our results suggest that both moderate-intensity exercise with a 30-g preexercise glucose beverage or interspersed with intermittent high-intensity sprints may be safe strategies to prevent hypoglycemia in glargine/glulisine users.

Nutritional strategies to prevent hypoglycemia at exercise in diabetic adolescents.

UNLABELLED: Studies on nutritional strategies to prevent exercise-induced hypoglycemia in adolescents with type 1 diabetes are scarce. OBJECTIVE: This study aimed to compare the effect of two food strategies on blood glucose (BG) during and after 60 min of moderate-intensity exercise. METHODS: Subjects performed exercise 120 min after breakfast in three conditions: 1) standardized breakfast + preexercise placebo beverage (PL), 2) standardized breakfast + preexercise CHO beverage (8 mg of CHO·kg of body weight·min of exercise; CHO), or 3) protein-supplemented breakfast (8 mg of protein·kg of body weight·min of exercise added to the standardized breakfast) + preexercise placebo beverage (PROT). As soon as BG falls <4 mmol·L or symptomatic hypoglycemia occurred during exercise, the session was stopped and CHO tablets were provided to correct hypoglycemia. RESULTS: Ten subjects (age = 14.0 ± 1.5 yr) participated in all conditions. BG decreased by 6.0 ± 1.9, 1.0 ± 3.1, and 4.6 ± 1.9 mmol·L in PL, CHO, and PROT conditions, respectively (P < 0.05). The proportion of subjects reaching hypoglycemic values or sensations of hypoglycemia was significantly different between conditions with 4/10, 1/10, and 0/10 in the PL, CHO, and PROT conditions (P < 0.05). CONCLUSIONS: The preexercise CHO beverage induced the least dramatic BG decrease during exercise. The PROT breakfast induced an overall similar BG drop compared to PL, a larger BG drop compared to CHO, but a similar rate of hypoglycemia compared to CHO. Our results suggest that taking CHO supplement before unplanned exercise is still the best strategy to prevent exercise-induced hypoglycemia in an adolescent population. However, a protein supplement strategy may also have some benefits in limiting the rate of hypoglycemia during and immediately after exercise.

Carbohydrate supplementation and sex differences in fuel selection during exercise.

PURPOSE: To compare the effects of a high-CHO diet (80% CHO) and glucose ingestion (2 g x kg(-1)) during exercise (120 min, 57% VO2max) on fuel selection in women taking (W+OC) or not (W-OC) oral contraceptives and in men (six in each group). METHODS: Substrate oxidation was measured using indirect respiratory calorimetry in combination with a tracer technique to compute the oxidation of exogenous (13C-glucose) and endogenous CHO. RESULTS: In the control situation (mixed diet with water ingestion during exercise), the percent contribution to the energy yield (%En) of CHO oxidation was higher in men than in women (62 vs 53 %En). The high-CHO diet and glucose ingestion during exercise separately increased the %En from CHO oxidation in both men (+12%) and women (+24%), and the sex difference observed in the control situation disappeared. However, the increase in the %En from total CHO oxidation observed when glucose was ingested during exercise and when combined with a high-CHO diet was larger in women than in men (+47 vs +17 %En). This was not attributable to a higher %En from exogenous glucose oxidation in women, for which no sex difference was observed (25 and 27 %En in men and women), but was attributable to a smaller decrease in endogenous glucose oxidation. No significant difference in fuel selection was observed between W+OC and W-OC. CONCLUSIONS: The increase in total CHO oxidation after the high-CHO diet was not different between sexes. Glucose ingestion during exercise, separately and combined to the high-CHO diet, had a greater effect in women than in men; this was mostly attributable to the smaller reduction in endogenous CHO oxidation.

Fuel selection and cycling endurance performance with ingestion of [13C]glucose: evidence for a carbohydrate dose response.

Endurance performance and fuel selection while ingesting glucose (15, 30, and 60 g/h) was studied in 12 cyclists during a 2-h constant-load ride [approximately 77% peak O2 uptake] followed by a 20-km time trial. Total fat and carbohydrate (CHO) oxidation and oxidation of exogenous glucose, plasma glucose, glucose released from the liver, and muscle glycogen were computed using indirect respiratory calorimetry and tracer techniques. Relative to placebo (210+/-36 W), glucose ingestion increased the time trial mean power output (%improvement, 90% confidence limits: 7.4, 1.4 to 13.4 for 15 g/h; 8.3, 1.4 to 15.2 for 30 g/h; and 10.7, 1.8 to 19.6 for 60 g/h glucose ingested; effect size=0.46). With 60 g/h glucose, mean power was 2.3, 0.4 to 4.2% higher, and 3.1, 0.5 to 5.7% higher than with 30 and 15 g/h, respectively, suggesting a relationship between the dose of glucose ingested and improvements in endurance performance. Exogenous glucose oxidation increased with ingestion rate (0.17+/-0.04, 0.33+/-0.04, and 0.52+/-0.09 g/min for 15, 30, and 60 g/h glucose), but endogenous CHO oxidation was reduced only with 30 and 60 g/h due to the progressive inhibition of glucose released from the liver (probably related to higher plasma insulin concentration) with increasing ingestion rate without evidence for muscle glycogen sparing. Thus ingestion of glucose at low rates improved cycling time trial performance in a dose-dependent manner. This was associated with a small increase in CHO oxidation without any reduction in muscle glycogen utilization.

Fuel selection during prolonged arm and leg exercise with 13C-glucose ingestion.

PURPOSE: To compare fuel selection during prolonged arm (AE) and leg exercise (LE) with water or glucose ingestion. METHODS: Ten subjects (VO2max: 4.77 +/- 0.20 and 3.36 +/- 0.15 L x min(-1) for LE and AE, respectively) completed 120 min of LE and AE at 50% of the mode-specific maximal power output (353 +/- 18 and 160 +/- 9 W, respectively) with ingestion of water (20 mL x kg(-1)) or 13C-glucose (2 g x kg(-1)). Substrate oxidation was measured using indirect respiratory calorimetry corrected for urea excretion and 13CO2 production at the mouth. RESULTS: The contribution of protein oxidation to the energy yield (%En) was higher during AE than LE (approximately 8% vs approximately 4%) because of the lower energy expenditure and was not significantly modified with glucose ingestion. With water ingestion, the %En from CHO oxidation was not significantly different during LE and AE (64 +/- 2% and 66 +/- 2%, respectively). Glucose ingestion significantly increased the %En from total CHO oxidation during AE (78 +/- 3%) but not during LE (71 +/- 2%). Exogenous glucose oxidation was not significantly different in AE and LE (56 +/- 4 and 65 +/- 3 g, respectively), but the %En from exogenous glucose was higher during AE than LE (30 +/- 1% and 24 +/- 1%) because of the lower energy expenditure. When glucose was ingested, the %En from endogenous CHO oxidation was significantly reduced during both AE (66 +/- 2% to 48 +/- 3%) and LE (64 +/- 2% to 47 +/- 3%) and was not significantly different in the two modes of exercise. CONCLUSIONS: The difference in fuel selection between AE and LE when water was ingested was modest with a slightly higher reliance on CHO oxidation during AE. The amount of exogenous glucose oxidized was lower but its %En was higher during AE because of the lower energy expenditure.

Comparison of exogenous glucose, fructose and galactose oxidation during exercise using 13C-labelling.

Six subjects exercised for 120 min on a cycle ergometer (65 (se 3) % VO2max) when ingesting a placebo or glucose, fructose or galactose (100 g in 1000 ml water) labelled with 13C. The oxidation of energy substrates including exogenous hexoses was compared using indirect respiratory calorimetry and 13CO2 production at the mouth. Total carbohydrate progressively decreased and total fat oxidation increased over the 120 min exercise period in the four experimental situations. During the 120 min of exercise, the amount of fructose oxidized (38.8 (se 2.6) g; 9.0 (se 0.6) % energy yield) was not significantly (approximately 4 %) lower than that of exogenous glucose (40.5 (se 3.4) g; 9.2 (se 0.8) % energy yield), while that of galactose (23.7 (se 3.5) g; 5.5 (se 0.9) % energy yield) was only 59 % and 61 % that of glucose and fructose, respectively. When compared with the placebo, the ingestion and oxidation of the three hexoses did not significantly modify fat oxidation or total carbohydrate oxidation, but it significantly reduced (9-13 %) endogenous carbohydrate oxidation. The present data indicate that fructose and exogenous glucose ingested during exercise could be oxidized at a similar rate, but that the oxidation rate of galactose was only approximately 60 % that of the exogenous glucose and fructose, presumably because of a preferential incorporation of galactose into liver glycogen (Leloir pathway). The reduction in endogenous carbohydrate oxidation was, however, similar with the three hexoses.

Glucagon receptors: effect of exercise and fasting.

One paradox of hormonal regulation during exercise is the maintenance of glucose homeostasis after endurance training despite a lower increase in plasma glucagon. One explanation could be that liver sensitivity to glucagon is increased by endurance training. Glucagon exerts its effect through a 62 KDa glycoprotein receptor, member of the G protein-coupled receptor. To determine whether changes with exercise in glucagon sensitivity occurred at the level of the glucagon receptor (GR), binding characteristics of hepatic glucagon receptors were ascertained in rat purified plasma membranes. Saturation kinetics indicated no difference in the dissociation constant or affinity of glucagon receptor, but a significantly higher glucagon receptor binding density in liver in endurance trained compared to untrained animals. Along with endurance training, it appears that fasting also changes GR binding characteristics. In animals fasting 24 hrs, a significant increase in glucagon receptor density was also reported. Although the exact mechanism remains unknown, there is no doubt that the liver can adapt to physiological stress through modulation of GR binding characteristics to enhance the hepatic glucose production responsiveness to glucagon.

Alterations in hepatic glucagon receptor density and in Gsalpha and Gialpha2 protein content with diet-induced hepatic steatosis: effects of acute exercise.

The present study was undertaken to test the hypothesis that a high-fat diet-induced liver lipid infiltration is associated with a reduction of hepatic glucagon receptor density (B(max)) and affinity (K(d)), and with a decrease in stimulatory G protein (G(s)alpha) content while enhancing inhibitory G protein (G(i)alpha(2)) expression. We also hypothesized that, under this dietary condition, a single bout of endurance exercise would restore hepatic glucagon receptor parameters and G protein expression to standard levels. Female Sprague-Dawley rats were fed either a standard (SD) or a high-fat diet (HF; 40% kcal) for 2 wk (n = 20 rats/group). Each dietary group was thereafter subdivided into a nonexercised (Rest) and an acute-exercised group (Ac-Ex). The acute exercise consisted of a single bout of endurance exercise on a treadmill (30 min, 26 m/min, and 0% slope) immediately before being killed. The HF compared with the SD diet was associated with significantly (P < 0.05) higher values in hepatic triglyceride concentrations (123%), fat pad weight, and plasma free fatty acid (FFA) concentrations. The HF diet also resulted in significantly (P < 0.05) lower hepatic glucagon receptor density (45%) and G(s)alpha protein content (75%), as well as higher (P < 0.05) G(i)alpha(2) protein content (27%), with no significant effects on glucagon receptor affinity. Comparisons of all individual liver triglyceride and B(max) values revealed that liver triglycerides were highly (P < 0.003) predictive of the decreased glucagon receptor density (R = -0.512). Although the 30-min exercise bout resulted in some typical exercise effects (P < 0.05), such as an increase in FFA (SD diet), a decrease in insulin levels, and an increase in plasma glucagon concentrations (SD diet), it did not change any of the responses related to liver glucagon receptors and G proteins, with the exception of a significant (P < 0.05) decrease in G(i)alpha(2) protein content under the HF diet. The present results indicate that the feeding of an HF diet is associated with a reduction in plasma membrane hepatic glucagon receptor density and G(s)alpha protein content, which is not attenuated by a 30-min exercise bout. It is suggested that liver lipid infiltration plays a role in reducing glucagon action in the liver through a reduction in glucagon receptor density and glucagon-mediated signal transduction.

Metabolic response to prolonged cycling with (13)C-glucose ingestion following downhill running.

The purpose of this study was to describe the effect of muscle damage and delayed-onset muscle soreness (DOMS) on the metabolic response during a subsequent period of prolonged concentric exercise (120 min, approximately 61% V(.)O(2max), on a cycle ergometer), with ingestion of 3 g of (13)C-glucose/kg body mass. We hypothesized that the oxidation of plasma and exogenous glucose would be reduced, while the oxidation of glucose arising from muscle glycogen would be increased. Six male subjects were studied during exercise in a control situation and 2 days following downhill running, at a time when plasma creatine kinase (CK) activity was increased, and DOMS was present. Carbohydrate and lipid oxidation were computed from indirect respiratory calorimetry corrected for protein oxidation, while the oxidation of plasma glucose and muscle glycogen were computed from V(.)(13)CO(2) and the ratio of (13)C/(12)C in the plasma glucose. All data were presented as the mean and the standard error of the mean. The oxidation of protein (approximately 6% energy yield, in the control and the experimental trial), lipid (approximately 15 and approximately 18%), and carbohydrate (approximately 79 and approximately 76%), as well as that of plasma glucose (approximately 41 and approximately 46%), glucose from the liver (approximately 12 and approximately 14%), and glucose from muscle glycogen (approximately 38 and approximately 31%) were not significantly different between the control and experimental (DOMS) trials. The response of the plasma glucose, insulin, lactate, and free fatty acid concentrations was not modified by the previous eccentric exercise. These results indicate that the metabolic response to prolonged concentric exercise is not modified by muscle damage and DOMS resulting from a bout of eccentric exercise performed 2 days before.

Partitioning oxidative fuels during cold exposure in humans: muscle glycogen becomes dominant as shivering intensifies.

The effects of changes in shivering intensity on the relative contributions of plasma glucose, muscle glycogen, lipids and proteins to total heat production are unclear in humans. The goals of this study were: (1) to determine whether plasma glucose starts playing a more prominent role as shivering intensifies, (2) to quantify overall changes in fuel use in relation to the severity of cold exposure, and (3) to establish whether the fuel selection pattern of shivering is different from the classic fuel selection pattern of exercise. Using a combination of indirect calorimetry and stable isotope methodology, fuel metabolism was monitored in non-acclimatized adult men exposed for 90 mins to 10 degrees C (low-intensity shivering (L)) or 5 degrees C (moderate-intensity shivering (M)). Results show that plasma glucose oxidation is strongly stimulated by moderate shivering (+122% from L to M), but the relative contribution of this pathway to total heat generation always remains minor (< 15% of total heat production). Instead, muscle glycogen is responsible for most of the increase in heat production between L and M. By itself, the increase in CHO oxidation is responsible for the 100 W increase in metabolic rate observed between L and M, because rates of lipid and protein oxidation remain constant. This high reliance on CHO is not compatible with the well known fuel selection pattern of exercise, when considering the relatively low metabolic rates elicited by shivering (approximately 30% for M). We conclude that shivering and exercise of similar energy requirements appear to be supported by different fuel mixtures. Investigating the physiological mechanisms underlying why a muscle producing only heat (shivering), or significant movement (exercise), shows a different pattern of fuel selection at the same power output strikes us as a fascinating area for future research.

Gender difference in the metabolic response to prolonged exercise with [13C]glucose ingestion.

The metabolic response to a 120-min cycling exercise with ingestion of [(13)C]glucose (3 g kg(-1)) was compared in women in the follicular phase of the cycle [ n=6; maximum rate of oxygen uptake (VO(2max)) 44.7 (2.6) ml kg(-1) min(-1)] and in men [ n=6; VO(2max) 54.2 (4.3) ml kg(-1) min(-1)] working at the same relative workload (approximately 65% VO(2max): 107 and 179 W in women and men, respectively). We hypothesized that the contribution of endogenous substrate oxidations (indirect respiratory calorimetry corrected for protein oxidation) to the energy yield will be similar in men and women, but that women will rely more than men on exogenous glucose oxidation. Over the exercise period, the respective contributions of protein, lipid and carbohydrate oxidation to the energy yield, were similar in men [3.7 (0.9), 21.7 (2.9) and 74.6 (3.5)%] and women [3.4 (0.8), 21.5 (2.2), 75.1 (2.5)%]. The rate of exogenous glucose oxidation was approximately 45% lower in women than men (0.5 and 0.6 g min(-1) vs 0.7 and 0.9 g min(-1), between min 40 and 80, and min 80 and 120, respectively). However, when the approximately 39% difference in absolute workload and energy expenditure was taken into account, the contribution of exogenous glucose oxidation to the energy yield was similar in men and women: 22.5 vs 24.2% between min 40 and 80, and 25.7 and 28.5% between min 80 and 120, respectively. These data indicate that when fed glucose, the respective contributions of the oxidation of the various substrates to the energy yield during prolonged exercise at the same % VO(2max) are similar in men and in women in the follicular phase of the cycle.