Carole Lavoie

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°C (low‐intensity shivering (L)) or 5°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 (∼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.

Increased hepatic glucose production response to glucagon in trained subjects

This study was designed to characterize the impact of endurance training on the hepatic response to glucagon. We measured the effect of glucagon on hepatic glucose production (HGP) in resting trained (n = 8) and untrained (n = 8) healthy male subjects (maximal rate of O2 consumption: 65.9 +/- 1.6 vs. 46.8 +/- 0.6 ml O2.kg-1.min-1, respectively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 micrograms/h) over 4 h. Insulin (0.15 mU.kg-1.min-1) was infused throughout the study, and glucagon (1.5 ng.kg-1.min-1) was infused over the last 2 h. During the latter period, plasma glucagon and insulin remained constant at 138.2 +/- 3.1 vs. 145.3 +/- 2.1 ng/l and at 95.5 +/- 4.5 vs. 96.2 +/- 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 +/- 1.1 mmol/l in trained subjects and at 8.9 +/- 0.8 mmol/l in untrained subjects (P < 0.001). During glucagon stimulation, the mean increase in HGP area under the curve was 15.8 +/- 2.8 mol.kg-1.min-1 in trained subjects compared with 7.4 +/- 1.6 mol.kg-1.min-1 in untrained subjects (P < 0.01) over the first hour and declined to 6.8 +/- 2.8 and 4.9 +/- 1.4 mol.kg-1.min-1 during the second hour. In conclusion, these observations indicate that endurance training is associated with an increase in HGP in response to physiological levels of glucagon, thus suggesting an increase in hepatic glucagon sensitivity.This study was designed to characterize the impact of endurance training on the hepatic response to glucagon. We measured the effect of glucagon on hepatic glucose production (HGP) in resting trained ( n = 8) and untrained ( n = 8) healthy male subjects (maximal rate of O2 consumption: 65.9 ± 1.6 vs. 46.8 ± 0.6 ml O2 ⋅ kg-1 ⋅ min-1, respectively, P < 0.001). Endogenous insulin and glucagon were suppressed by somatostatin (somatotropin release-inhibiting hormone) infusion (450 μg/h) over 4 h. Insulin (0.15 mU ⋅ kg-1 ⋅ min-1) was infused throughout the study, and glucagon (1.5 ng ⋅ kg-1 ⋅ min-1) was infused over the last 2 h. During the latter period, plasma glucagon and insulin remained constant at 138.2 ± 3.1 vs. 145.3 ± 2.1 ng/l and at 95.5 ± 4.5 vs. 96.2 ± 1.9 pmol/l in trained and untrained subjects, respectively. Plasma glucose increased and peaked at 11.4 ± 1.1 mmol/l in trained subjects and at 8.9 ± 0.8 mmol/l in untrained subjects ( P < 0.001). During glucagon stimulation, the mean increase in HGP area under the curve was 15.8 ± 2.8 mol ⋅ kg-1 ⋅ min-1in trained subjects compared with 7.4 ± 1.6 mol ⋅ kg-1 ⋅ min-1in untrained subjects ( P < 0.01) over the first hour and declined to 6.8 ± 2.8 and 4.9 ± 1.4 mol ⋅ kg-1 ⋅ min-1during the second hour. In conclusion, these observations indicate that endurance training is associated with an increase in HGP in response to physiological levels of glucagon, thus suggesting an increase in hepatic glucagon sensitivity.

Metabolic response to small and large 13 C-labelled pasta meals following rest or exercise in man

The metabolic response to a 150 or 400 g 13C-labelled pasta meal was studied for 8 h following rest or exercise at low or moderate workload (n 6). Following rest, the 400 g meal totally suppressed fat oxidation (v. 14.1 g following the 150 g meal) and a small amount of glucose was converted into fat (4.6 g), but fat oxidation remained high in subjects who had exercised following both the small (21.8 and 34.1 g) and large meal (14.1 and 32.3 g). Exogenous glucose oxidation was significantly higher in subjects who had remained at rest both following the small (67.6 g v. 60.4 and 51.3 g in subjects who exercised at low and moderate workloads) and large meal (152.2 v. 123.0 and 127.2 g). Endogenous glucose oxidation was similar in the three groups following the 150 g meal (42.3-58.0 g), but was significantly lower following the 400 g meal in subjects who had exercised at low workload (24.2 v. 72.2 g following rest; and was totally suppressed in those who had exercised at moderate workload. As a consequence, a larger positive glycogen balance was observed in subjects who exercised before the large meal (182.8-205.1 g v. 92.4 g following rest; Total fat oxidation calculated from 08.00 hours to 20.00 hours was similar in subjects who exercised at low and moderate workloads. These results indicate that: (1) de novo lipogenesis, which plays only a minor role for the disposal of an acute dietary carbohydrate load, is totally suppressed following exercise, even when a very large carbohydrate load is ingested; (2) the reduction in glycogen turnover as well as a preferential conversion of glucose into glycogen are responsible for the increase in glycogen stores following exercise; (3) for a similar energy expenditure, exercise at low workload for a longer period does not favour fat oxidation when the post-exercise period is taken into account.

Carbon isotope fractionation between blood and expired CO2 at rest and exercise

Carbon isotope fractionation occurs between bicarbonates and gaseous CO2. Accordingly, expired CO2 could be impoverished in 13C vs. blood CO2 (approximately 90% bicarbonates). The ratio 13C/12C in expired and blood CO2 was measured in six healthy subjects at rest and at the end of exercise (90 min; 65+/-5% VO2max), with ingestion of water (300 ml) without or with glucose (30 g) naturally or artificially enriched in 13C, in order to study a range of 13C/12C in blood (-17.5+/-0.3 to 3.4+/-0.6% delta 13C PDB-1). At rest, 13C/12C in expired CO2 was 4.7+/-0.2% delta 13C PDB-1 lower than in blood CO2. This difference was not modified in response to exercise with ingestion of water or 13C-glucose (average difference 4.6+/-0.4 % delta 13C PDB-1). Carbon isotope fractionation across the lung was approximately 30% lower than predicted from the fractionation factor between bicarbonates and gaseous CO2 (1.00674 at 37 degrees C, or a approximately 6.6% delta 13C PDB-1 difference). This is consistent with the fact that approximately 40% of expired CO2 is released from carbamates and dissolved CO2. From a methodological point of view, these results indicate that 13C/12C in expired CO2 adequately tracks 13C/12C in blood CO2 with a constant approximately 4.6 % delta 13C PDB-1 difference.

Use of an α‐glucosidase inhibitor to maintain glucose homoeostasis during postprandial exercise in intensively treated Type 1 diabetic subjects

Aim  We evaluated the effects of an α‐glucosidase inhibitor, acarbose, on glucose homoeostasis during postprandial exercise in Type 1 diabetic subjects.

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.

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.

Liver glucagon receptor binding properties: rapid changes with exercise and post-exercise

The purpose of this study was to describe the effects of swimming exercise and post-exercise periods on liver glucagon receptor (GR) binding properties. Rats were randomly assigned to a rest control, a swimming exercise (90and 180-min) and post-exercise (60and 180-min) groups. Rats were sacrificed at the end of the exercise or the post-exercise periods, blood was sampled and liver was removed rapidly. Plasma membranes were purified from liver and saturation kinetics were obtained by incubation (10 mg of proteins/150 mL) with ()I-labeled glucagon at concentrations ranging from 0.15 to 3.0 nM for 30 min at 30°C. results: No changes were observed with blood glucose during exercise and post-exercise periods, even if hepatic glycogen concentrations were significantly depleted with both exercise and post-exercise periods. Saturating curve analysis indicated higher glucagon receptor density with exercise reaching after 180 min: Bmax = 8.19 ± 0.29 pmol/pg of proteins vs 3.09 ± 0.53 pmol/pg of proteins in liver from resting control (P < 0.05). The glucagon receptor density decreased in post-exercise to reach 4.46 ± 1.75 pmol/pg of proteins after 180 min of post-exercise. Moderate changes in glucagon receptor affinity were also observed in the exercise and post-exercise groups compared to the control group (Kd at 180 min exercise and post-exercise: 0.46 ± 0.05 and 0.17 ± 0.01 vs 0.33 ± 0.05 nM in the rest control group). At the pancreatic hormone levels, these binding properties changes were associated with an increase in glucagon/insulin ratio of x2.8 and x8.7 during 90 and 180 min exercise periods and x9.3 and x2.7 after 60 and 180 min postexercise periods vs the rest control group. conclusion: these results suggest that exercise and post-exercise episodes induced both changes in insulin and glucagon concentrations and rapid modification in glucagon receptor binding properties. Although the exact mechanisms remain unknown, there is no doubt that the liver adapt rapidly to exercise through modulation of GR binding characteristics. Funded by Natural Sciences and Engineering Research Council of Canada.

Hepatic Glucagon Receptor In Rats: Effect Of Type 1 Diabetes.

Hepatic Glucagon Receptor In Rats: Effect Of Type 1 Diabetes. JOHNATAN LAMANQUE*, JESSICA MORISSETTE, ALEXANDRE MELANCON, GENEVIEVE ROBERT, FRANCOIS PERONNET AND CAROLE LAVOIE. Universite du Quebec a Trois-Rivieres et Universite de Montreal, Quebec. The purpose of this study was to describe the density and binding properties of hepatic glucagon receptor in rats with insulin-treated type 1 diabetes (single injection of 80 mg/kg of streptozotocin i.p.). One week after the diabetes was established, and for the duration of the 8week experimentation period, blood glucose concentration was normalized by subcutaneous insulin 7-mm long implants. No difference was observed for weight (435 ± 15 and 423 ± 7 g) and blood glucose concentration (7.0 ± 1.2 and 7.7 ± 0.6 mmol/L) for the diabetes (n = 6) and control groups (n = 5) at the time of sacrifice. Plasma membranes were purified from liver, and saturation kinetics were obtained by incubation with ()I-labelled glucagon. Saturating curves analysis indicated a similar glucagon receptor density in liver from diabetic and control animals (Bmax = 3.38 ± 0.48 and 3.09 ± 0.12 pmol/mg of proteins), but the affinity of the receptor was lower in diabetic rats (Kd = 1.02 ± 0.10 vs 0.33 ± 0.05 nM). These preliminary results suggest that in liver from type 1 diabetic rats treated with insulin, the density of hepatic glucagon receptor is normal but their affinity is lower than in liver from control animals. This finding could partly explain the lost of glucagon sensibility acquired with type 1 diabetes. Supported by Diabete Trois-Rivieres, Diabete-Quebec and NSERC. ABSTRACT #78