Increased Glycogen Storage Research Articles

Orphan Receptor Small Heterodimer Partner Is an Important Mediator of Glucose Homeostasis

The orphan receptor small heterodimer partner (SHP; NROB2) is a transcriptional repressor that inhibits nuclear receptor signaling in diverse metabolic pathways. Here, we report that SHP(-/-) mice exhibited hypoinsulinemia with age, which was associated with increased peripheral insulin sensitivity and increased response of isolated islets to glucose stimulation, yet maintain normal levels of blood glucose. Deficiency in SHP function resulted in up-regulation of glucose transporter 4 mRNA and glucose uptake in muscles, and overexpression of SHP in C2C12 cells inhibited both basal and peroxisomal proliferator-activated receptor gamma (PPARgamma) coactivator-1alpha-stimulated glucose transporter 4 expression and glucose uptake. SHP(-/-) hepatocytes showed markedly decreased basal glucose production in cultures, and SHP(-/-) livers had increased glycogen stores and were more sensitive to insulin inhibition of glucose output, which were concomitant with decreased expression for PPARgamma1, fatty acid translocase, glucose-6-phosphatase, and phosphoenol/pyruvate carboxykinase, and increased mRNAs for glucokinase and pyruvate kinase. In white fat, SHP deficiency resulted in up-regulation of genes involved in insulin sensitizing, including PPARgamma2 and adiponectin. We show that, at the transcriptional level, SHP directly represses adiponectin promoter activity by PPARgamma/liver receptor homolog-1. The results suggest that the increases in insulin sensitivity through multiple signaling pathways in muscle, liver, and fat, with an increase in islet secretory function, represent the complex mechanism whereby SHP deficiency leads to improvement in insulin sensitivity, secretion, and diabetes.

Increased glycogen storage in yeast results in less branched glycogen

Glycogen is a branched polymer of glucose, synthesized as a reserve of both energy and carbon. The branched nature of glycogen is important for its function and polyglucosan bodies, particles that contain a glycogen-like polymer with reduced branching, are a feature of several disease states. The degree of glycogen branching is thought to be governed by the balance between glycogen synthesis and branching activities. However, there have been reports that the intrinsic properties of individual branching enzymes govern the degree of branching. To address the relationship between synthesis and branching more fully, we made use of the yeast Saccharomyces cerevisiae. The glycogen content of yeast cells was manipulated by using different growth conditions or by the introduction of specific mutations. Whenever glycogen storage was elevated, the polysaccharide formed was found to be less branched but normal branching could be restored by overexpression of branching enzyme.

Effect of Systemic Hypoxia on GLUT4 Protein Expression in Exercised Rat Heart

Altitude training is a common method used to enhance endurance performance in athletes. We have examined the interactive effect of exercise training and chronic hypoxic on glycogen storage and GLUT4 protein expression in cardiac muscles. Thirty-two male Sprague-Dawley rats were weight balanced and assigned to one of the following four groups: control, exercise, hypoxia, and hypoxia-exercise. Rats with hypoxic treatment (breathing 14% O(2) for 12 hr/d) were exposed under normobaric conditions. The training protocol consisted of swimming for two 3-hr periods per day for 4 weeks. Glycogen content, GLUT4 protein, and mRNA of all rats were determined 16 hr after treatments. Four-week exercise training without hypoxia significantly elevated myocardial glycogen level by 45%. The chronic hypoxic-exercise training elevated the myocardial glycogen level by 67% above control level, significantly greater than the exercise group. Chronic hypoxia, exercise training, and hypoxia-exercise training significantly elevated GLUT4 protein by 40-70% in cardiac muscles. Chronic hypoxia significantly elevates the GLUT1 protein level independent of exercise training. The new finding in this study was that GLUT4 gene expression in cardiac muscle can be stimulated by exercise training with hypoxia treatments. This molecular adaptation appears to be associated with the observed increase in glycogen storage of the muscle.

Vitamin C Is an Important Cofactor for Both Adrenal Cortex and Adrenal Medulla

The adrenal gland is among the organs with the highest concentration of vitamin C in the body. Interestingly, both the adrenal cortex and the medulla accumulate such high levels of ascorbate. Ascorbic acid is a cofactor required both in catecholamine biosynthesis and in adrenal steroidogenesis. Here we provide an overview on the role of vitamin C in the adrenal cortex and medulla derived from in vitro and in vivo studies. In addition, recent insights gained from an animal model with a deletion in the gene for the ascorbic acid transporter will be summarized. Mutant mice lacking the plasma membrane ascorbic acid transporter (SVCT2) have severely reduced tissue levels of ascorbic acid and die soon after birth. There is a significant decrease of tissue catecholamine levels in the adrenals. On the ultrastructural level, adrenal chromaffin cells in SVCT2 null mice show depletion of catecholamine storage vesicles, signs of apoptosis, and increased glycogen storage. Decreased plasma levels of corticosterone and altered morphology of mitochondrial membranes indicate additional effects of the deficiency on adrenal cortical function. The data derived from these animal models and various cell culture studies confirm a crucial role for vitamin C for both the adrenal cortex as well as the adrenal medulla further underlining the interdependence of the two endocrine systems united in one gland.

Sensory meat quality, ultimate pH values, blood parameters and carcass characteristics in reindeer (Rangifer tarandus tarandus L.) grazed on natural pastures or fed a commercial feed mixture

Sensory properties in meat, ultimate muscle pH values, blood metabolites and carcass characteristics from reindeer grazed on natural pasture (n=23) or fed a commercial feed mixture (n=17) were studied. Reindeer fed commercial feed generally had lower ultimate pH values (increased glycogen stores) in all three muscles measured (Mm. triceps brachii, longissimus and biceps femoris) compared with the animals grazing natural pasture. Raised plasma urea concentrations in all reindeer were explained by a relatively high intake of protein for both treatments. Aspartate aminotransferase (ASAT) activities in all animals were low, and did not indicate muscle degeneration due to stress. However, the measured plasma cortisol concentrations showed that all reindeer were affected by the immediate pre-slaughter handling. Sensory evaluation was performed both as a descriptive test using a selected and trained panel, and as a preference test carried out with two groups of consumers (experienced and non-experienced reindeer meat eaters). The trained panel concluded that meat from reindeer fed commercial feed scored higher for liver and sweet flavour intensities and lower for off-flavour compared with meat from reindeer grazing natural pasture. The consumer test showed no effect of consumer age, gender or residence on the preference for meat from reindeer on either feed. The importance for the reindeer industry to acknowledge and use the differences in flavour and consumer preference as a specialised marketing strategy for reindeer meat is discussed.

Elucidation of the role of fructose 2,6-bisphosphate in the regulation of glucose fluxes in mice usingin vivo13C NMR measurements of hepatic carbohydrate metabolism

Fructose 2,6-bisphosphate (Fru-2,6-P2) plays an important role in the regulation of major carbohydrate fluxes as both allosteric activator and inhibitor of target enzymes. To examine the role of Fru-2,6-P2 in the regulation of hepatic carbohydrate metabolism in vivo, Fru-2,6-P2 levels were elevated in ADM mice with adenovirus-mediated overexpression of a double mutant bifunctional enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (n = 6), in comparison to normal control mice (control, n = 6). The rates of hepatic glycogen synthesis in the ADM and control mouse liver in vivo were measured using new advances in 13C NMR including 3D localization in conjunction with [1-13C]glucose infusion. In addition to glycogen C1, the C6 and C2-C5 signals were measured simultaneously for the first time in vivo, which provide the basis for the estimation of direct and indirect synthesis of glycogen in the liver. The rate of label incorporation into glycogen C1 was not different between the control and ADM group, whereas the rate of label incorporation into glycogen C6 signals was in the ADM group 5.6 +/- 0.5 micro mol.g-1.h-1, which was higher than that of the control group of 3.7 +/- 0.5 micro mol.g-1.h-1 (P < 0.02). The rates of net glycogen synthesis, determined by the glycogen C2-C5 signal changes, were twofold higher in the ADM group (P = 0.04). The results provide direct in vivo evidence that the effects of elevated Fru-2,6-P2 levels in the liver include increased glycogen storage through indirect synthesis of glycogen. These observations provide a key to understanding the mechanisms by which elevated hepatic Fru-2,6-P2 levels promote reduced hepatic glucose production and lower blood glucose in diabetes mellitus.

Melatonin and the wintering strategy of the tundra vole, Microtus oeconomus.

Short photoperiod induces physiological changes connected to the wintering of the tundra vole, Microtus oeconomus. The aim of the present study was to investigate the effects of continuous melatonin treatment on selected hormones and enzyme activities associated with energy metabolism in the species. Liver, kidney, and muscle glycogen concentrations and glycogen phosphorylase activities, as well as liver and kidney glucose-6-phosphatase and lipase esterase activities were determined. Plasma leptin, ghrelin, thyroxine, testosterone, cortisol, and melatonin concentrations were also measured. Exogenous melatonin stimulated gluconeogenesis, increased glycogen stores, and reduced fat mobilization in kidneys. Melatonin treatment also increased the food intake of the voles. This may have been mediated via elevated ghrelin levels of the melatonin-treated animals, as ghrelin is known to increase appetite of rodents. Winter metabolism of the species does not seem to require accumulation of fat or extra stores of liver or muscle glycogen. On the contrary, successful wintering of the tundra vole presumably depends on continuous food availability.

Effects of fasting and exogenous glucose delivery on cardiac tolerance to low-flow ischemia in adult and senescent rats

Metabolic disorders due to changes in cytosolic glucose utilisation are suspected to be involved in the increased sensitivity of the aged myocardium to ischemia. This study presents the first direct measurement of glucose utilisation in hearts from senescent rats during low-flow ischemia under different conditions of substrate delivery and glycogen stores. Isolated hearts from young adult (4-months-old) and senescent (24-months-old) rats were subjected to 30 min coronary flow restriction (residual flow rate=2% of control flows). Experiments were performed using glucose-free or glucose-enriched (11 mmol/L) perfusion media. The effects of increased glycogen stores were assessed after 24-h fasting in both age groups. Ischemic contracture was measured via a left-ventricular balloon. Ageing increased ischemic contracture under both conditions of substrate delivery in fed rat hearts. The increase in ischemic tolerance induced by fasting in senescent rat hearts was less than that seen in young rat hearts. Moreover, fasting decreased glucose utilisation in hearts from young rats, an effect which was not found in hearts from old rats. Furthermore, myocardial glycogen utilisation was increased in all groups of aged rats compared with that of young adults, particularly under fasting conditions. It is concluded that fasting is less detrimental to the aged myocardium during low-flow ischemia than to the young myocardium because it does not further reduce exogenous glucose utilisation, and it stimulates glycogen consumption. Moreover, a reduction in exogenous glucose utilisation, which is only partly compensated for by increased glycogenolytic flux could be, at least in part, responsible for the increased ischemic contracture in hearts from old fed rats. Finally, our glucose-free experiments suggest that residual oxidative phosphorylation during low-flow ischemia might be less relevant in hearts from senescent rats than in those from young adults.

Glucose uptake in malignant tumors of the head and neck

Positron emission tomography (PET) studies have shown an elevated glucose uptake in squamous cell carcinomas of the head and neck (HNSCC). On a cellular level glucose uptake is mediated by specific glucose transport proteins. We have used immunohistochemistry ot study the expression of different facilitative glucose transport proteins (GLUT) in the normal mucosa and in HNSCC. A weak expression of GLUT 1 was observed in epithelial cells of the normal mucosa. However, the expression of GLUT 1 was strongly elevated in epithelial cells of HNSCC. GLUT2, 3 and 4 were not detected in any of the epithelial tissues examined. An increased expression of GLUT 3 was found in inflammatory cells. The storage of glycogen showed a negative correlation to the GLUT 1 expression. While an increased glycogen storage was accompanied by a decreased GLUT 1 expression in highly differentiated epithelial cells, glycogen loss was associated with a strong GLUT 1 expression in less differentiated cells. The present study with PET indicates that the elevated glucose uptake of HNSCC is closely related to an increased expression of GLUT 1 in epithelial tumor cells.

Effects of conditioning horses with lactate-guided exercise on muscle glycogen content.

The effects of 3 different conditioning programmes on muscle glycogen concentration in horses were examined. Speed of exercise was selected according to the blood lactate values for each horse derived from a standardised exercise test before beginning a conditioning programme. Six 2-year-old Haflinger stallions were assigned randomly to one of 3 conditioning programmes according to a 6 x 3 latin square design: 45 min at their individual v1.5 or v2.5 and 25 min at v4. Each conditioning programme lasted 6 weeks (21 exercise sessions), followed by 5 weeks without conditioning (resting period). All exercise was carried out on a treadmill inclined at 17%. Muscle biopsies were taken 5 times from the gluteus medius muscle at 2 cm and 6 cm depth: before the start and in the middle of the conditioning period, then at Days 2, 9 and 35 after the last exercise session. It was found that glycogen concentration was not affected by conditioning until 9 days after finishing conditioning at v1.5 and v2.5 for 45 min (P < 0.05). By this time glycogen concentration in the muscle samples taken at 6 cm depth increased by 47 and 48%, respectively, and remained elevated until the end of the resting period. It was concluded that conditioning at lower intensity and for longer duration seemed to increase glycogen stores in the muscle while faster intensity but shorter duration exercise did not. To increase the likelihood of measuring effects of conditioning programmes on muscle variables, sampling should be done at different depths of a muscle and at several days after finishing a conditioning programme.

Effective nutritional ergogenic aids.

Athletes use a variety of nutritional ergogenic aids to enhance performance. Most nutritional aids can be categorized as a potential energy source, an anabolic enhancer, a cellular component, or a recovery aid. Studies have consistently shown that carbohydrates consumed immediately before or after exercise enhance performance by increasing glycogen stores and delaying fatigue. Protein and amino acid supplementation may serve an anabolic role by optimizing body composition crucial in strength-related sports. Dietary antioxidants, such as vitamins C and E and carotenes, may prevent oxidative stress that occurs with intense exercise. Performance during high-intensity exercise, such as sprinting, may be improved with short-term creatine loading, and high effort exercise lasting 1-7 min may be improved through bicarbonate loading immediately prior to activity. Caffeine dosing before exercise delays fatigue and may enhance performance of high-intensity exercise.

The improved incorporation of polyunsaturated fatty acids and changes in liver structure in larval gilthead seabream fed on microdiets

Two feeding experiments were conducted to evaluate the suitability of two commercial microdiets as a complementary food for the rearing of larval gilthead seabream Sparus aurata. The effect of these diets on growth, survival and total lipid composition, as well as the histological structure of the liver were examined. The results of the first trial highlighted water quality as an important factor for the survival of microdiet‐fed larvae. An increase in water flow rate improved larval survival despite a reduction in live food supply. An effect of tank design on larval growth and survival was observed also and seems to be related with the light level inside the tanks; wider light grey tanks gave better results than narrower black ones. Microdiet feeding significantly improved larval growth and increased hepatocyte diameter and presence of PAS positive vacuoles suggesting an increased glycogen storage in comparison with that of larvae fed live prey only. Artificial diets provided the larvae with a higher amount of lipids and polyunsaturated fatty acids of the n‐3 series, resulting in a higher DHA content in the total lipid of the larvae fed on microdiets.

Subacute toxicity of ergometrine maleate in rats

Ergot alkaloids, produced by the fungus Claviceps purpurea, are found in small amounts in foodstuffs. The human disease ergotism, caused by high intake of ergot alkaloids, is well known; however, little is known about the toxicity of these compounds. The subacute toxicity of an ergot alkaloid, ergometrine maleate, was therefore studied. Sprague-Dawley rats were treated with 0, 2, 10, 50 and 250 mg ergometrine maleate/kg diet for 4 wk. Plasma glucose levels were decreased in females at 50 and 250 mg/kg. Thyroxin levels were decreased at 50 (males only) and 250 mg/kg. At the high dose level, organ weights of heart, liver, ovaries and kidneys were increased. In male rats a slight dose-related increase in the incidence of enlarged mediastinal lymph nodes and, to some extent, of enlarged parathymal lymph nodes, was seen. Histopathological examination revealed evidence of increased glycogen storage in the liver of animals treated with 250 mg/kg. The no-observed-effect level in this study was 10 mg/kg.

Muscle phosphofructokinase deficiency in two generations

Phosphofructokinase (PFK) is the key regulatory enzyme of glycolysis. Patients lacking the muscular isoform of PFK typically present with myopathy and compensated hemolysis (glycogenosis type VII or Tarui's disease). Since 1965 about 30 cases of muscular PFK deficiency have been reported. In most cases family history suggests a recessive inherited trait. We describe a family of Ashkenazi Jewish origin with two members in subsequent generations suffering from muscular PFK deficiency. The propositus, a 19-year-old male patient, presented with weakness, myalgias and exercise intolerance since early infancy. His father also had early fatigue on exercise with myalgias; the mother and a 12-year-old brother were asymptomatic. Muscle biopsy of both the propositus and his father showed increased glycogen storage and absent histochemical stain for PFK. Biochemical studies of muscle revealed a markedly decreased PFK activity and DNA analysis of the muscle PFK gene revealed compound heterozygosity in both cases. This is the first description of proven muscle PFK deficiency (glycogenosis type VII) in two subsequent generations.

Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed and skeletal muscle.

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.

Effect of diet and training on muscle glycogen storage and utilization in sled dogs.

Two groups of eight Alaskan huskies fed either a high-fat (HFD; 60% kcal from fat and 15% kcal from carbohydrate) or a high-carbohydrate diet (HCD; 60% kcal from carbohydrate and 15% kcal from fat) performed standard aerobic (1 h at 4 m/s on a 0% slope) and anaerobic (3 min at 6.7 m/s on a 10% slope) tests before and after training. Before and immediately after each exercise test, venous blood samples were collected and analyzed for lactate and pyruvate, and muscle biopsies were obtained under local anesthesia from the semitendinosus muscle and analyzed for total muscle glycogen (TMG) concentration. Training was associated with a significant increase in preexercise TMG in both diet groups; this effect was most marked in the HCD. There was no effect of diet or training on TMG utilization during the aerobic tests. The rate of TMG utilization during the anaerobic tests was between 20 and 40 times greater than that measured during the aerobic tests. The pre- to postexercise change in TMG was dependent on preexercise TMG in the HCD and HFD for both anaerobic tests (HCD: P < 0.01, r = 0.81; HFD: P < or = 0.03, r = 0.66). It is concluded that the increased glycogen storage associated with the HCD was more than offset by the more rapid rate of glycogen utilization in this group. HFD facilitated carbohydrate sparing during intense exercise and should thus be a better dietary strategy for endurance in sled dogs.

Loss of hepatic autoregulation after carbohydrate overfeeding in normal man.

To determine the effect of increased glycogen stores on hepatic carbohydrate metabolism, 15 nondiabetic volunteers were studied before and after 4 d of progressive overfeeding. Glucose production and gluconeogenesis were assessed with [2-3H] glucose and [6-14C] glucose (Study I, n = 6) or [3-3H] glucose and [U-14C]-alanine (Study II, n = 9) and substrate oxidation was determined by indirect calorimetry. Overfeeding was associated with significant (P < 0.01) increases in plasma glucose (4.97 +/- 0.10 to 5.09 +/- 0.11 mmol/liter), insulin (18.8 +/- 1.5 to 46.6 +/- 10.0 pmol/liter) and carbohydrate oxidation (4.7 +/- 1.4 to 18.0 +/- 1.5 mumol.kg-1.min-1) and a decrease in lipid oxidation (1.2 +/- 0.2 to 0.3 +/- 0.1 mumol.kg-1.min-1). Hepatic glucose output (HGO) increased in Study I (10.2 +/- 0.5 to 13.1 +/- 0.9 mumol.kg-1.min-1, P < 0.01) and Study II (11.17 +/- 0.67 to 13.33 +/- 0.83 mumol.kg-1.min-1, P < 0.01), and gluconeogenesis decreased (57.6 +/- 6.4 to 33.4 +/- 4.9 mumol/min, P < 0.01), indicating an increase in glycogenolysis. The increase in glycogenolysis was only partly compensated by an increase in glucose cycle activity (2.2 +/- 0.2 to 3.4 +/- 0.4 mumol.kg-1.min-1, P < 0.01) and the fall in gluconeogenesis, thus resulting in increased HGO. The suppression of gluconeogenesis despite increased lactate and alanine (glycerol was decreased) was associated with decreased free fatty acid (FFA) oxidation and negligible FFA enhanced gluconeogenesis. These studies suggest that increased liver glycogen stores alone can overwhelm normal intrahepatic mechanisms regulating carbohydrate metabolism resulting in increased HGO in nondiabetic man.

Liver and peripheral tissue glycogen metabolism in obese mice: effect of a mixed meal

Glycogen metabolism in the liver, skeletal muscle, cardiac muscle, and white adipose tissue was studied in gold thioglucose (GTG) obese mice after fasting and during refeeding. Prolonged (48 h) fasted control and GTG mice were refed with standard laboratory diet for 24 h. During fasting and refeeding, the changes in glycogen content and the activity of glycogen synthase I and R and phosphorylase alpha in the liver were similar in lean and GTG mice. However, the glycogen storage in the livers from GTG mice was always greater than that in lean animals. In GTG mice the activity of liver glycogen synthase I and R was significantly higher than that in lean animals 3 and 6 h after refeeding. The activity of liver phosphorylase alpha in GTG mice was higher than that in lean mice after refeeding. There were no significant differences in the glycogen content of white adipose tissue, cardiac muscle, and skeletal muscle from lean and GTG mice during the entire study. The results of this study suggest that increased glycogen storage in the liver is a major alteration in nonoxidative glucose metabolism and contributes to the development of insulin resistance and glucose intolerance in GTG obese mice.

Effects of glycogen stores and non-esterified fatty acid availability on insulin-stimulated glucose metabolism and tissue pyruvate dehydrogenase activity in the rat

The effects of increased tissue glycogen stores on insulin sensitivity, and on the response of insulin-stimulated glucose utilisation to an acute elevation in plasma fatty acid levels (approximately 1.5 mmol/l), were investigated in conscious rats using the hyperinsulinaemic euglycaemic clamp. Studies were performed in two groups of rats; (a) fasted 24 h; (b) fasted 4.5 h, but infused with glucose for 4 h (0.5 g/h) of this period before the clamp (fed, glucose infused rats). Clamp glucose requirement and 3-3H-glucose turnover were 20-25% lower in the fed, glucose-infused rats. In these rats, elevation of plasma fatty acid levels resulted in impaired suppression of hepatic glucose output (residual hepatic glucose output: 41 +/- 4 vs 8 +/- 6 mumol.min-1.kg-1, p less than 0.001) but did not further decrease 3-3H-glucose turnover. Elevated non-esterified fatty acid levels had no significant effect on glucose kinetics in 24 h fasted rats. In the fed glucose-infused rats, at low plasma fatty acid levels, there was no deposition of glycogen in muscle during the clamp and liver glycogen levels fell. With elevation of non-esterified fatty acid levels muscle glycogen deposition was stimulated in both groups, and there was no fall in liver glycogen during the clamps in the fed glucose-infused rats. Increased non-esterified fatty acid availability during the clamps decreased pyruvate dehydrogenase activity in liver, heart, adipose tissue and quadriceps muscle, in both groups of rats. The findings are consistent with an inhibition of glycolysis in liver, skeletal muscle and heart by increased fatty acid availability.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolic fuel utilization during postexercise recovery

The postexercise recovery period is characterized by transition from the acutely catabolic phase that occurs during exercise to an anabolic phase. Muscle glycogen stores are replenished after exercise and even in the absence of refeeding have returned to 50% of preexercise concentrations within 12 h (1). The increase in net protein degradation that is demonstrable during exercise at low-to-moderate workboads is replaced by net protein resynthesis as soon as exercise is stopped (2, 3). These anabobic responses are essential for physical training to result in increased glycogen stores and lean body mass. Physical training programs have been advocated as an important component in the treatment of subjects with noninsulin-dependent diabetes mellitus (NIDDM). Physical training was shown to improve the major defect present in NIDDM, ie, peripheral insulin resistance (4), and to improve glycemic control in these subjects (5). How much ofthis beneficial effect ofregular physical exercise is due to the cumulative effects of single bouts of exercise vs a specific training effect has been unclear. Recent work suggests that benefits may be demonstrable after single bouts ofexercise (6, 7) and the training effect is rapidly lost when an exercise program is interrupted (7, 8). Although most exercise studies have focused on effects on peripheral (skeletal muscle) insulin sensitivity, hepatic glucose production may also be affected by exercise(6). Although postexercise recovery is characterized by overall anabobic responses, these responses may vary in different body compartments. Ahlborg et al (9) showed that nonexercised muscle demonstrates ongoing catabolism (glycogenolysis) during the early postexercise period (40 mm) with release ofbactate presumably for gluconeogenesis. Whether this differential response (catabolism in nonexercised muscle, anabolism in exercised muscle) occurs for longer periods and involves other gluconeogenic precursors requires further study. Finally, food ingestion during exercise was shown to enhance endurance exercise performance in some studies ( 10) but not in others ( 11). Preexercise glucose ingestion may adversely affect performance (1 2). We (13) studied the effects of preexercise ingestion of a mixedmeal snack on the metabolic fuel responses during and after exercise. Subjects for the studies conducted during the bate (1216 h) postexercise recovery period consisted of six male control subjects within 18% of ideal body weight (14), designated as lean for the purpose of the study; six male subjects > 130% ideal body weight with either glucose intolerance or hyperinsubinemia during a 75-g oral glucose tolerance test ( 15), designated as obese; and five male subjects with NIDDM (1 5) who were all > 1 18% ideal body weight. Subjects for the studies conducted during early (2-4 h) postexercise recovery consisted of 1 1 lean healthy subjects (6 male, 5 female). For the studies of the effects of preexercise snack feeding, nine healthy male subjects within 15% of ideal body weight were selected. Except for obesity and diabetes melbitus in the respective groups, all subjects were deemed to be in excellent health as determined by medical history, physicab examination, and laboratory screening chemistry studies.