Metabolic and hormonal responses to prolonged physical exercise in dogs after a single fat-enriched meal

Metabolic and hormonal responses to prolonged treadmill exercise in dogs fed a fat-enriched meal 4 h prior to the exercise were compared to those measured 4 h after a mixed meal or in the postabsorptive state. Ingestion of the fat-enriched meal caused significant elevations in the resting values of plasma triglyceride (TG), free fatty acid (FFA), and glycerol concentrations. A reduction of the plasma TG concentration (from 1.6 +/- 0.2 to 1.1 +/- 0.10 mmol X l-1, P less than 0.005) occurred only in dogs exercising after the fat-enriched meal. No significant changes in this variable were noted in dogs fed a mixed meal, whilst in the postabsorptive state exercise caused an increase in the plasma TG level (from 0.42 +/- 0.03 to 0.99 +/- 0.11 mmol X l-1, P less than 0.01). The exercise-induced elevations in plasma FFA and glycerol concentrations were the highest in the dogs given the fat-enriched meal. Plasma glycerol during exercise correlated with the initial values of circulating TG (r = 0.73). The plasma FFA-glycerol ratio, at the end of exercise was lowest in the dogs taking the fat-enriched meal (1.39 +/- 0.19), suggesting an increased utilization of FFA in comparison with that in the postabsorptive state (3.27 +/- 0.37) or after a mixed meal (2.88 +/- 0.55). Basal serum insulin (IRI) concentrations were similarly enhanced in dogs fed fat-enriched and mixed meals, and they were reduced to control values within 60 min of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of thyroxine treatment on metabolic responses to a single insulin injection

Metabolic responses to a single i.v. injection of cristalline insulin (0.2 i.u./kg b.w.) were compared in control and T4-treated dogs both at rest and after prolonged physical exercise. The post-insulin decrease in blood glucose was significantly correlated with the pre-insulin BG concentration. Thus, the insulin-induced fall of BG was greatest in T4-treated dogs at rest, in which significantly higher BG levels were found in comparison with controls, and smallest in the same dogs after exercise, i.e. at the lowest initial BG concentrations. The post-insulin hypoglycaemia caused marked increases in the plasma FFA level in control dogs, both at rest and after physical effort, and in T4-treated dogs at rest. They were accompanied by elevations in the plasma adrenaline levels. In T4-treated dogs given insulin after exercise decreases both in the plasma FFA and A concentrations were found. In the majority of the control and T4-treated dogs insulin injected at rest caused an increase in blood LA levels, being more pronounced in the latter. Insulin injected after physical exercise did not change blood LA level in T4 treated dogs, and it caused its decrease in the control animals. The results of these investigations show that both T4-treatment and physical exercise, performed prior to insulin injection, modify the metabolic response to insulin and post-insulin hypoglycaemia.     

Effect of elevated FFA on carbohydrate and lipid oxidation during prolonged exercise in humans

Increased availability of circulating free fatty acids (FFA) inhibits the rate of glycolysis in heart and resting skeletal muscle (Randle effect). Whether elevated FFA may play a role in decreasing carbohydrate oxidation during prolonged exercise in humans is more controversial. Using respiratory exchange measurements, we measured substrate utilization during 2.5 h of exercise at approximately 44 +/- 1% maximal O2 uptake (VO2 max) in the presence or absence of elevated FFA levels. After 30 min of base-line determinations, 1,000 U heparin was given intravenously and a 3-h constant infusion of Intralipid 10% (150 g/h) and heparin (500 U/h) was started. After an additional 30 min of rest, subjects exercised for 2.5 h (study 1, n = 6). In another five subjects (study 2) 100 g glucose was ingested after 30 min of exercise. The same protocols (studies 1 and 2) were also performed during a 0.9%-saline infusion. During exercise, without glucose ingestion, higher FFA concentrations prevailed during the Intralipid infusion (1,122 +/- 40 vs. 782 +/- 65 mumol/l), but the relative contributions of carbohydrate (49 +/- 4 vs. 50 +/- 4%) or lipid (49 +/- 4 vs. 47 +/- 6%) oxidation to the total energy expenditure were different only during the first 30 min of exercise. Similarly, higher FFA levels (1,032 +/- 62 vs. 568 +/- 46 mumol/l) did not alter the relative contributions of carbohydrate (62 +/- 4 vs. 69 +/- 2%) or lipid (36 +/- 4 vs. 29 +/- 2%) oxidation to the total energy expenditure after glucose feeding.(ABSTRACT TRUNCATED AT 250 WORDS)     

Shift in metabolic substrate uptake by the heart during development of alloxan-induced diabetes

Inhibition of endothelial nitric oxide (NO) synthase (eNOS) is associated with an increase in glucose uptake by the heart. We have already shown that Type I diabetes also causes a decrease in eNOS protein expression and altered NO control of both coronary vascular resistance and oxygen consumption. Therefore, we predict that the increase in plasma glucose and the reduction in eNOS during diabetes together would result in a large increase in cardiac glucose uptake. Arterial (A) and coronary sinus (C) plasma levels of glucose, free fatty acid (FFA), beta-hydroxybutyric acid (beta-HBA), and lactate were measured, and myocardial uptake was calculated before and at week 1, 2, 3, and 4 of alloxan-induced diabetes. The heart of healthy dogs consumed FFA (19.2 +/- 2.6 microeq/min) and lactate (19.7 +/- 3.4 micromol/min). Dogs in the late stage of diabetes (at week 4) had elevated arterial beta-HBA concentrations (1.6 +/- 0.7 micromol/l) that were accompanied by an increased beta-HBA uptake (0.3 +/- 0.2 micromol/min). In contrast, myocardial lactate (-4.8 +/- 3.0 micromol/min) and FFA uptake (2.5 +/- 1.9 microeq/min) were significantly reduced in diabetic animals. Despite a marked hyperglycemia (449 +/- 25 mg/dl), the heart did not take up glucose (-7.9 +/- 4.1 mg/dl). Our results indicate significant changes in the myocardial substrate utilization in dogs only in the late stage of diabetes, at a time when myocardial NO production is already decreased.     

Cardiac triacylglycerol content and lipase activity during recovery from exercise

Female rats swam for 2-h to determine the temporal relationship between triglyceride (TG) repletion and TG lipase activity in the heart during recovery from exercise. Immediately after the exercise, plasma free fatty acids (FFA) had increased from a resting value of 0.44 +/- 0.04 to 0.84 +/- 0.04 mM. Heart TG concentration was reduced 75%, whereas the glycogen level was decreased 34% below control. TG lipase activity was elevated 33% above control activity. One hour after the end of the exercise, lipolytic activity was still 26% above control and did not return to the resting level until the 4th h of recovery. The cardiac TG concentration was back to control levels by the 2nd h after the swim. Plasma FFA concentrations remained elevated during the first 4 h of recovery and were back to the control level by h 8. Cardiac glycogen was "supercompensated" during recovery h 1 and 2 and returned to the preexercise level by h 4. These data indicate that TG is being synthesized in the heart while lipolytic enzyme activity is elevated above control levels. This points out that the rate of TG synthesis is in excess of the hydrolysis. Since plasma FFA concentrations are elevated during periods of augmented TG synthesis, substrate availability, namely plasma FFA, may play a key role in regulating the size of the intracellular TG pool.     

Progressive enhancement of body temperature responses to consecutive exercise-bouts of the same intensity in dogs

Progressive enhancement of body temperature responses to consecutive exercise-bouts of the same intensity in dogs. Acta physiol. pol., 1985, 36 (3): 165-174. Changes in rectal (Tre), muscle (Tm), and hypothalamic (Thy) temperatures, plasma osmolality, and some intermediary metabolic variables were examined in dogs performing four successive exercise-bouts of the same intensity. During the rest-intervals separating the exercise-bouts body temperatures returned to initial levels and water losses were replaced. Tm and Tre responses to consecutive exercise-bouts were progressively increasing. Similar tendency was found in Thy changes. Cardiac and respiratory frequencies attained the same levels in all four exercise-bouts, while blood lactate and FFA concentrations were increasing and blood glucose level was decreasing progressively. No changes in plasma osmolality was noted. Exercise-induced increases in Tm correlated positively with plasma FFA concentration (r = 0.68). Body temperature responses to exercise were reduced by beta-adrenergic blockade. It is concluded that the enhancement of the thermal responses to consecutive exercise-bouts can be related to the metabolic action of catecholamines.     

Metabolic responses to catecholamines in dogs injected with a single dose of triiodothyronine.

Lipolytic and glycogenolytic responses to catecholamine infusions were studied in resting dogs before and 20 h following administration of a single dose (0.1 mg/kg) of triiodothyronine (T3). In the dogs pretreated with T3 much higher increases in the plasma FFA concentration were found both during noradrenaline and adrenaline infusions in comparison with control experiments. Adrenaline-induced increases in blood LA and glucose levels were also significantly higher in T3-pretreated dogs than in controls. The blockade of beta-adrenergic receptors with propranolol prevented the increases in blood FFA and LA concentrations during subsequent adrenaline infusion. Phentolamine -- the alpha-adrenergic blocking agent -- infused to the T3-pretreated dog inhibited the adrenaline-induced rise in blood glucose level. The observed changes in the metabolic responses to catecholamines induced by triiodothyronine pretreatment indicate that at least in the dog this hormone potentiates both the lipolytic and glycogenolytic effects of catecholamines acting on appropriate adrenergic receptors.     

Glucose and lactate turnover and gluconeogenesis in chronic metabolic acidosis and alkalosis in normal and diabetic dogs

The turnover rate of glucose, the irreversible disposal rate of lactate, and the rate of gluconeogenesis from lactate were calculated by tracer methods in four normal and four alloxan-diabetic dogs under control conditions as well as in chronic, stable metabolic acidosis and alkalosis. Acidosis was produced by feeding dogs 0.8-1 g.kg-1.day-1NH4Cl over 1 week, alkalosis was produced by feeding dogs a chloride-free diet and injections of furosemide. Mean plasma pH in the three states were 7.28 +/- 0.013, 7.40 +/- 0.024, and 7.51 +/- 0.015 in normal dogs, and 7.22 +/- 0.025, 7.42 +/- 0.009, and 7.49 +/- 0.002 in the diabetic dogs. Respective mean plasma bicarbonate levels were 14.6 +/- 0.88, 22.0 +/- 0.80, and 32.4 +/- 1.88 mequiv. in normal dogs, and 12.3 +/- 1.30, 22.6 +/- 0.66, and 35.0 +/- 1.14 mequiv. in diabetic animals. In normal dogs shifts in acid-base balance had no effect on the level of plasma glucose or the turnover rate of glucose. In diabetic dogs plasma glucose level was significantly elevated by alkalosis. Plasma lactate was positively correlated with plasma pH (r = 0.69, p less than 0.01) and was in general higher in diabetic than in normal animals. The increment in concentration was due to a decreased clearance of lactate from the plasma. The irreversible disposal rate was not changed by the acid-base status. Whereas a larger fraction of lactate removed from the plasma appeared in glucose in diabetic animals, this fraction was not changed significantly by shifts in the acid-base status.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute anemia results in an increased glucose dependence during sustained exercise

We evaluated whether acute anemia results in altered blood glucose utilization during sustained exercise at 26.8 m/min on 0% grade, which elicited approximately 60-70% maximal O2 consumption. Acute anemia was induced in female Sprague-Dawley rats by isovolumic plasma exchange transfusion. Hemoglobin and hematocrit were reduced 33% by exchange transfusion to 8.6 +/- 0.4 g/dl and 26.5 +/- 1%, respectively. Glucose kinetics were determined by primed continuous infusion of [6-3H]glucose. Rates of O2 consumption were similar during rest (pooled means 25.1 +/- 1.8 ml.kg-1.min-1) and exercise (pooled means 46.8 +/- 3.0 ml.kg-1.min-1). Resting blood glucose and lactate concentrations were not different in anemic animals (pooled means 5.1 +/- 0.2 and 0.9 +/- 0.02 mM, respectively). Exercise resulted in significantly decreased blood glucose (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and elevated lactate (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM) concentrations in anemic animals. Glucose turnover rates (Rt) were not different between anemic and control animals at rest and averaged 58.8 +/- 3.6 mumol.kg-1.min-1. Exercise resulted in a 30% greater increase in Rt in anemic (141.7 +/- 3.2 mumol.kg-1.min-1) than in control animals (111.2 +/- 5.2 mumol.kg-1.min-1). Metabolic clearance rates (MCR = Rt/[glucose]) were not different at rest (11.6 +/- 7.4) but were significantly greater in anemic (55.2 +/- 5.7 ml.kg-1.min-1) than in control animals (24.3 +/- 1.4 ml.kg-1.min-1) during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of diazepam treatment on metabolic indices in trained and untrained rats

Exercise training, like diazepam, is commonly employed as a means of reducing anxiety. Both diazepam and exercise training have been shown to modify carbohydrate and lipid metabolism as well as influence calcium metabolism in skeletal muscle. As receptor binding and thereby efficacy of diazepam has been demonstrated to be modulated by the lipid environment of the receptor, and changes in calcium levels can affect a number of intracellular signalling pathways, we sought to determine if the interaction of both chronic diazepam and exercise training would modify selected metabolic indices in an animal model. For this purpose, muscle and liver glycogen, blood glucose and plasma free fatty acids (FFA) were measured in sedentary, exercise trained and exercise trained, acutely exhausted animals. Alterations in lipid and carbohydrate metabolism were observed in all experimental groups. Diazepam treatment alone exerts metabolic consequences, such as elevated muscle glycogen and plasma FFA and depressed blood glucose levels, which are similar to those observed with exercise training. When animals are acutely exercised to exhaustion, however, differences appear, including a reduced rise in plasma FFA, which suggests that long-term diazepam treatment does influence exercise metabolism, possibly as a result of effects on the sympatho-adrenal system.     

Acute anemia increases lactate production and decreases clearance during exercise

We evaluated whether elevated blood lactate concentration during exercise in anemia is the result of elevated production or reduced clearance. Female Sprague-Dawley rats were made acutely anemic by exchange transfusion of plasma for whole blood. Hemoglobin and hematocrit were reduced 33%, to 8.6 +/- 0.4 mg/dl and 26.5 +/- 1.1%, respectively. Blood lactate kinetics were studied by primed continuous infusion of [U-14C]lactate. Blood flow distribution during rest and exercise was determined from injection of 153Gd- and 113Sn-labeled microspheres. Resting blood glucose (5.1 +/- 0.2 mM) and lactate (1.9 +/- 0.02 mM) concentrations were not different in anemic animals. However, during exercise blood glucose was lower in anemic animals (4.0 +/- 0.2 vs. 4.6 +/- 0.1 mM) and lactate was higher (6.1 +/- 0.4 vs. 2.3 +/- 0.5 mM). Blood lactate disposal rates (turnover measured with recyclable tracer, Ri) were not different at rest and averaged 136 +/- 5.8 mumol.kg-1.min-1. Ri was significantly elevated in both control (260.9 +/- 7.1 mumol.kg-1.min-1) and anemic animals (372.6 +/- 8.6) during exercise. Metabolic clearance rate (MCR = Ri/[lactate]) did not differ during rest (151 +/- 8.2 ml.kg-1.min-1); MCR was reduced more by exercise in anemic animals (64.3 +/- 3.8) than in controls (129.2 +/- 4.1). Plasma catecholamine levels were not different in resting rats, with pooled mean values of 0.45 +/- 0.1 and 0.48 +/- 0.1 ng/ml for epinephrine (E) and norepinephrine (NE), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of glucose on plasma glucagon and free fatty acids during prolonged exercise

The effects of glucose ingestion on the changes in blood glucose, FFA, insulin and glucagon levels induced by a prolonged exercise at about 50% of maximal oxygen uptake were investigated. Healthy volunteers were submitted to the following procedures: 1. a control test at rest consisting of the ingestion of 100 g glucose, 2. an exercise test without, or 3. with ingestion of 100 g of glucose. Exercise without glucose induced a progressive decrease in blood glucose and plasma insulin; plasma glucagon rose significantly from the 60th min onward (+45 pg/ml), the maximal increase being recorded during the 4th h of exercise (+135 pg/ml); plasma FFA rose significantly from the 60th min onward and reached their maximal values during the 4th h of exercise (2177 +/- 144 muEq/l, m +/- SE). Exercise with glucose ingestion blunted almost completely the normal insulin response to glucose. Under these conditions, exercise did not increase plasma glucagon before the 210th min; similarly, the exercise-induced increase in plasma FFA was markedly delayed and reduced by about 60%. It is suggested that glucose availability reduces exercise-induced glucagon secretion and, possibly consequently, FFA mobilization.     

Hemodynamic and metabolic responses to exercise after adrenoceptor blockade in humans

The effects of acute alpha 1-adrenoceptor blockade with prazosin, beta 1-adrenoceptor blockade with atenolol, and nonselective beta-adrenoceptor blockade with propranolol were compared in a placebo-controlled crossover study of the hemodynamic and metabolic responses to acute exercise 2 h after prolonged prior exercise to induce skeletal muscle glycogen depletion, enhancing the dependence on hepatic glucose output and circulating free fatty acids (FFA). Plasma catecholamines were higher during exercise after, as opposed to before, glycogen depletion and were elevated further by all three drugs. Propranolol failed to produce a significant reduction in systolic blood pressure and elevated diastolic blood pressure. Atenolol reduced systolic blood pressure and did not change diastolic blood pressure. Both beta-blockers reduced FFA levels, but only propranolol lowered plasma glucose relative to placebo during exercise after glycogen depletion. In contrast, prazosin reduced systolic and diastolic blood pressures and resulted in elevated FFA and glucose levels. The results indicate important differences in the hemodynamic effects of beta 1-selective vs. nonselective beta-blockade during exercise after skeletal muscle glycogen depletion. Furthermore they confirm the importance of beta 2-mediated hepatic glucose production in maintaining plasma glucose levels during exercise. Acute alpha 1-blockade with prazosin induces reflex elevation of catecholamines, which in the absence of blockade of hepatic beta 2-receptors produces elevation of plasma glucose. The results suggest there is little role for alpha 1-mediated hepatic glucose production during exercise in humans.     

Retardant effect of hyperglycemia on the rise in plasma fatty acids following insulin withdrawal in man

The present study was undertaken to examine the influence of hyperglycemia in retarding the rise in circulating FFA noted after acute insulin withdrawal in man. The arterial FFA response to somatostatin administration was measured in the presence of (a) euglycemia and (b) hyperglycemia. In seven normal men who received somatostatin (0.9 mg/h) with euglycemia maintained by exogenous glucose infusion plasma insulin levels fell to levels 4 uU/ml and plasma FFA concentrations rose from 659 +/- 123 to 2057 +/- 268 uEq/l. When somatostatin was infused with hyperglycemia maintained at approximately 230 mg/dl, plasma insulin levels were again maintained at levels 4 uU/ml. Despite similar insulinopenia plasma FFA concentrations rose from 510 +/- 56 to only 1125 +/- 180 uEq/l, significantly less than in the previous protocol (p less than 0.01). These data indicate that hyperglycemia per se significantly attenuates the rise in circulating FFA caused by acute insulin withdrawal in man.     

Effect of propranolol on thyroxine-induced changes in body temperature and metabolism during exercise in dogs.

Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s.c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (Tre) during exercise as early as 5h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest Tre, blood FFA and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in Tre and blood LA concentrations during the next 30 min of exercise.     

Plasma beta endorphin immunoreactivity: effects of sustained hyperglycemia with and without prior exercise

Seven healthy untrained men were studied to determine if sustained hyperglycemia is a stimulus to enhanced plasma levels of beta endorphin (beta-EP) and if so whether prior exercise affects that enhancement. After an overnight fast hyperglycemic glucose clamps were performed on 3 separate days: after prior rest, 2 h after exercise, and 48 h after exercise. Subjects exercised on a bicycle ergometer for 1 h at 150 W (64% VO2 max). Plasma glucose concentration was elevated in 4 continuous sequential stages to 7, 11, 20 and 35 mM with each stage lasting 90 min. Plasma glucose concentrations did not differ for each subject across the three clamps. beta-EP immunoreactivity was measured in arterialized venous blood samples using a specific and sensitive radioimmunoassay. Resting beta-EP at basal glucose concentrations was 3.8 +/- 0.7 fmol X ml-1 (mean +/- se) and prior exercise either 2h (3.2 +/- 0.5 fmol X ml-1) or 48 h (4.3 +/- 0.7 fmol X ml-1) before a clamp study did not effect these levels, (p greater than 0.05). At no time during the 3 hyperglycemic clamps did plasma levels of beta-EP differ significantly from resting values. At the highest level of hyperglycemia (35 mM) beta-EP was 3.1 +/- 0.2, 4.9 +/- 0.6 and 4.8 +/- 0.7 fmol X ml-1 in the resting, 2h and 48 h post exercise clamp studies respectively. The significance of these data is that this lack of a response is in distinct contrast to elevations of this peptide found during hypoglycemic states. We conclude that sustained hyperglycemia is not a stimulus to enhanced secretion of beta-EP into plasma and this lack of a response is not effected by prior exercise.     

Glucoregulation and hormonal responses to maximal exercise in non-insulin-dependent diabetes

Maximal dynamic exercise results in a postexercise hyperglycemia in healthy young subjects. We investigated the influence of maximal exercise on glucoregulation in non-insulin-dependent diabetic subjects (NIDDM). Seven NIDDM and seven healthy control males bicycled 7 min at 60% of their maximal O2 consumption (VO2max), 3 min at 100% VO2max, and 2 min at 110% VO2max. In both groups, glucose production (Ra) increased more with exercise than did glucose uptake (Rd) and, accordingly, plasma glucose increased. However, in NIDDM subjects the increase in Ra was hastened and Rd inhibited compared with controls, so the increase in glucose occurred earlier and was greater [147 +/- 21 to 169 +/- 19 (30 min postexercise) vs. 90 +/- 4 to 100 +/- 5 (SE) mg/dl (10 min postexercise), P less than 0.05]. Glucose levels remained elevated for greater than 60 min postexercise in both groups. Glucose clearance increased during exercise but decreased postexercise to or below (NIDDM, P less than 0.05) basal levels, despite increased insulin levels (P less than 0.05). Plasma epinephrine and glucagon responses to exercise were higher in NIDDM than in control subjects (P less than 0.05). By use of the insulin clamp technique at 40 microU.m-2.min-1 of insulin with plasma glucose maintained at basal levels, glucose disposal in NIDDM subjects, but not in controls, was enhanced 24 h after exercise. It is concluded that, because of exaggerated counter-regulatory hormonal responses, maximal dynamic exercise results in a 60-min period of postexercise hyperglycemia and hyperinsulinemia in NIDDM. However, this event is followed by a period of increased insulin effect on Rd that is present 24 h after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interaction of free fatty acids and epinephrine in regulating hepatic glucose production in conscious dogs

To determine the effects of an increase in lipolysis on the glycogenolytic effect of epinephrine (EPI), the catecholamine was infused portally into 18-h-fasted conscious dogs maintained on a pancreatic clamp in the presence [portal (Po)-EPI+FFA, n = 6] and absence (Po-EPI+SAL, n = 6) of peripheral Intralipid infusion. Control groups with high glucose (70% increase) and free fatty acid (FFA; 200% increase; HG+FFA, n = 6) and high glucose alone (HG+SAL, n = 6) were also included. Hepatic sinusoidal EPI levels were elevated (Delta 568 +/- 77 and Delta 527 +/- 37 pg/ml, respectively) in Po-EPI+SAL and EPI+FFA but remained basal in HG+FFA and HG+SAL. Arterial plasma FFA increased from 613 +/- 73 to 1,633 +/- 101 and 746 +/- 112 to 1,898 +/- 237 micromol/l in Po-EPI+FFA and HG+FFA but did not change in EPI+SAL or HG+SAL. Net hepatic glycogenolysis increased from 1.5 +/- 0.3 to 3.1 +/- 0.4 mg x kg(-1) x min(-1) (P < 0.05) by 30 min in response to portal EPI but did not rise (1.8 +/- 0.2 to 2.1 +/- 0.3 mg x kg(-1) x min(-1)) in response to Po-EPI+FFA. Net hepatic glycogenolysis decreased from 1.7 +/- 0.2 to 0.9 +/- 0.2 and 1.6 +/- 0.2 to 0.7 +/- 0.2 mg x kg(-1) x min(-1) by 30 min in HG+FFA and HG+SAL. Hepatic gluconeogenic flux to glucose 6-phosphate increased from 0.6 +/- 0.1 to 1.2 +/- 0.1 mg x kg(-1) x min(-1) (P < 0.05; by 3 h) and 0.7 +/- 0.1 to 1.6 +/- 0.1 mg x kg(-1) x min(-1) (P < 0.05; at 90 min) in HG+FFA and Po-EPI+FFA. The gluconeogenic parameters remained unchanged in the Po-EPI+SAL and HG+SAL groups. In conclusion, increased FFA markedly changed the mechanism by which EPI stimulated hepatic glucose production, suggesting that its overall lipolytic effect may be important in determining its effect on the liver.     

Metabolic and hormonal responses to exhaustive supramaximal running with and without beta-adrenergic blockade

The metabolic and hormonal responses to exhaustive short-term supramaximal exercise were studied in 10 male physical education students. The exercise task was a single bout of running on the treadmill at 22 km X h-1 and 7.5% slope. It was performed with single oral doses of 100 mg Bupranolol (non-selective beta-blockade), 100 mg Metoprolol (beta-1-selective blockade), and placebo. Arterialized capillary and venous blood were sampled until 30 min post exercise. Time to exhaustion was 52.0 +/- 2.6, 47.6 +/- 2.0, and 46.0 +/- 1.9 s in the control, Metroprolol, and Bupranolol experiments. At cessation of exercise, adrenaline and noradrenaline were grossly elevated in all three conditions. Lactate and glucose increased markedly, this being accompanied by increasing insulin in the control and Metoprolol, but not the Bupranolol trials. Glycerol increased moderately, while FFA were depressed. Growth hormone showed a delayed increase at 15 and 30 min post exercise. Cortisol was unaffected by exercise. beta-blockade reduced the increases of lactate, glucose, glycerol, insulin, and growth hormone, exaggerated the depression of FFA and had no effect on cortisol. The results demonstrate that the strong sympatho-adrenal response to exercise of this nature is a major determinant of the increase of glucose at cessation of exercise. The hyperglycemia in concert with beta-2-adrenergic stimulation leads to elevation of insulin. Furthermore, lipolysis is controlled by beta-adrenergic stimulation. The delayed increase of growth hormone seems to be triggered by the declining glucose level during recovery.     

Skeletal muscle basal AMP-activated protein kinase activity is chronically elevated in alloxan-diabetic dogs: impact of exercise.

The effect of diabetes and exercise on skeletal muscle (SkM) AMP-activated protein kinase (AMPK)alpha1 and -alpha2 activities and site-specific phosphorylation of acetyl-CoA carboxylase was examined in the same six dogs before alloxan (35 mg/kg)-induced diabetes (C) and after 4-5 wk of suboptimally controlled hyperglycemic and hypoinsulinemic diabetes (DHG) in the presence and absence of 300-min phlorizin (50 microg.kg-1.min-1)-induced "normoglycemia" (DNG). In each study, the dog underwent a 150-min [3-3H]glucose infusion period, followed by a 30-min treadmill exercise test (60-70% maximal oxygen capacity) to measure the rate of glucose disposal into peripheral tissues (Rdtissue). SkM biopsies were taken from the thigh (vastus lateralis) before and immediately after exercise. In the C and DHG states, the rise in plasma free fatty acids (FFA) with exercise ( approximately 40%) was similar. In the DNG group, preexercise FFA were significantly higher, but the absolute rise in FFA with exercise was similar. However, the exercise-induced increment in Rdtissue was significantly blunted (by approximately 40-50%) in the DNG group compared with the other states. In SkM, preexercise AMPKalpha1 and -alpha2 activities were significantly elevated (by approximately 60-125%) in both diabetic states, but unlike the C group these activities did not rise further with exercise. Additionally, preexercise acetyl-CoA carboxylase phosphorylation in both diabetic states was elevated by approximately 70-80%, but the increases with exercise were similar to the C group. Preexercise AMPKalpha1 and -alpha2 activities were negatively correlated with Rdtissue during exercise for the combined groups (both P < 0.02). In conclusion, the elevated preexercise SkM AMPKalpha1 and -alpha2 activities contribute to the ongoing basal supply of glucose and fatty acid metabolism in suboptimally controlled hypoinsulinemic diabetic dogs; but whether they also play a permissive role in the metabolic stress response to exercise remains uncertain.