The dynamic life of the glycogen granule.

Glycogen, the primary storage form of glucose, is a rapid and accessible form of energy that can be supplied to tissues on demand. Each glycogen granule, or "glycosome," is considered an independent metabolic unit composed of a highly branched polysaccharide and various proteins involved in its metabolism. In this Minireview, we review the literature to follow the dynamic life of a glycogen granule in a multicompartmentalized system, i.e. the cell, and how and where glycogen granules appear and the factors governing its degradation. A better understanding of the importance of cellular compartmentalization as a regulator of glycogen metabolism is needed to unravel its role in brain energetics.

An oral lipid challenge and acute intake of caffeinated coffee additively decrease glucose tolerance in healthy men.

Lipid-induced insulin resistance has been investigated primarily with i.v. infusions, and caffeine-induced insulin resistance, with alkaloid caffeine. The effects of orally consumed lipids and coffee have not been established and to our knowledge have never been simultaneously investigated. The goals of this study were to determine whether an oral lipid challenge and caffeinated coffee would disrupt glucose homeostasis and to characterize their respective incretin responses. It was hypothesized that oral ingestion of saturated lipids would impair glucose tolerance and that caffeinated coffee would further hinder glucose management. Ten young, healthy males participated in 5 trials in a randomized, cross-over design. At time 0 h, they underwent an oral fat tolerance test (OFTT: 1 g lipid/kg body weight) or consumed water, followed 5 h later by caffeinated (5 mg/kg) coffee, decaffeinated coffee, or water. At 6 h, volunteers underwent an oral glucose tolerance test (OGTT). Consumption of the OFTT increased glucose concentrations (P < 0.05) after a subsequent OGTT. At 7 h, caffeinated coffee produced the highest glucose concentrations (P < 0.05). Glucagon-like peptide-1 active (GLP-1a) and glucose-dependent insulinotropic polypeptide (GIP) were both increased for up to 6 h in all OFTT trials (P < 0.05). Compared to all other treatments, caffeinated and decaffeinated coffee produced higher GLP-1a response at 6.25 h (P < 0.05), whereas only caffeinated coffee increased GIP secretion (P < 0.05). These results show that oral consumption of lipids and caffeinated coffee can independently and additively decrease glucose tolerance. Incretin hormones could explain at least in part this impaired glucose homeostasis.

Methylxanthines and human health: epidemiological and experimental evidence.

When considering methylxanthines and human health, it must be recognized that in many countries most caffeine is consumed as coffee. This is further confounded by the fact that coffee contains many bioactive substances in addition to caffeine; it is rich in phenols (quinides, chlorogenic acid, and lactones) and also has diterpenes (fatty acid esters), potassium, niacin, magnesium, and the vitamin B(3) precursor trigonelline. There is a paradox as consumption of either caffeine or caffeinated coffee results in a marked insulin resistance and yet habitual coffee consumption has repeatedly been reported to markedly reduce the risk for type 2 diabetes. There is strong evidence that caffeine reduces insulin sensitivity in skeletal muscle and this may be due to a combination of direct antagonism of A(1) receptors and indirectly ß-adrenergic stimulation as a result of increased sympathetic activity. Caffeine may also induce reduced hepatic glucose output. With the exception of bone mineral, there is little evidence that caffeine impacts negatively on other health issues. Coffee does not increase the risk of cardiovascular diseases or cancers and there is some evidence suggesting a positive relationship for the former and for some cancers, particularly hepatic cancer.

Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males.

Caffeine and caffeinated coffee (CC) elicit acute insulin insensitivity when ingested before a carbohydrate load. The effects of CC on glucose tolerance and insulin sensitivity when co-ingested with a high carbohydrate meal and on postprandial metabolism of a subsequent (second) carbohydrate load have not been studied. In a randomised, crossover design, ten healthy males ingested either CC (5 mg caffeine/kg body weight), decaffeinated coffee (DC) or water (W; equal volume) co-ingested with a high glycaemic index cereal followed 3 h later by a 75 g oral glucose tolerance test. After the initial meal, insulin area under the curve (AUC) and insulin sensitivity index did not differ between treatments, although glucose AUC for CC (107 (sem 18) mmol/l x 3 h) and DC (74 (sem 15) mmol/l x 3 h) was greater than W ( - 0.2 (sem 29) mmol/l x 3 h, P < 0.05). After the second carbohydrate load, insulin AUC for CC was 49 % and 57 % greater (P < 0.01) than for DC and W, respectively. Despite the greater insulin response, glucose AUC for CC (217 (sem 24) mmol/l x 2 h) was greater than both DC (126 (sem 11) mmol/l x 2 h, P = 0.01) and W (55 (sem 34) mmol/l x 2 h, P < 0.001). Insulin sensitivity index after the second meal was lower after CC (8.2 (sem 0.9)) compared with both DC (12.4 (sem 1.2), P < 0.01) and W (13.4 (sem 1.4), P < 0.001). Co-ingestion of CC with one meal resulted in insulin insensitivity during the postprandial phase of a second meal in the absence of further CC ingestion. Thus, CC may play a role in daily glycaemic management.

The acute impact of ingestion of breads of varying composition on blood glucose, insulin and incretins following first and second meals.

Structural characteristics and baking conditions influence the metabolic responses to carbohydrate-containing foods. We hypothesized that consumption of whole wheat or sourdough breads would have a favourable effect on biomarkers of glucose homeostasis after first and second meals, compared with those for white bread. Ten overweight volunteers consumed 50 g available carbohydrate of each of the four breads (white, whole wheat, sourdough, whole wheat barley) followed 3 h later by a standard second meal. Blood was sampled for 3 h following bread ingestion and a further 2 h after the second meal for determination of glucose, insulin, paracetamol (indirect marker of gastric emptying), glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Glucose and GLP-1 responses to sourdough bread were lower (P < 0.05) than whole wheat and whole wheat barley breads. Glucose area under the curve (AUC) for sourdough bread was lower than those for whole wheat (P < 0.005) and whole wheat barley (P < 0.03) breads for the entire study. GIP AUC after sourdough bread ingestion was lower compared to white (P < 0.004) and whole wheat barley (P < 0.002) breads following the second meal. There were no significant differences in insulin and paracetamol concentrations among the test breads. Ultra-fine grind whole wheat breads did not result in postprandial responses that were lower than those of white bread, but sourdough bread resulted in lower glucose and GLP-1 responses compared to those of these whole wheat breads following both meals.

Acute caffeine ingestion and glucose tolerance in women with or without gestational diabetes mellitus.

OBJECTIVE: Recent work showing that caffeine impairs glucose tolerance may be of particular concern in pregnancy because of a possible negative effect on fetal outcome. The current study sought to assess the effect of acute caffeine ingestion on glucose tolerance in women with or without gestational diabetes mellitus (GDM). METHODS: Nineteen women whose routine GDM test was negative (control) and eight women with an initial positive GDM screen completed two trials one week apart in a double-blind randomized crossover study. Following an overnight fast, subjects ingested caffeine (3 mg/kg pre-pregnancy body weight) or an identical-appearing placebo (gelatin) capsule and one hour later began a 75 g 2-hour oral glucose tolerance test. RESULTS: In the control group, caffeine did not significantly affect blood glucose, insulin, or C-peptide. In the GDM group, glucose area under the curve (AUC) was greater (P < 0.01), C-peptide AUC was greater (P < 0.05), and insulin sensitivity index was lower (18%, P < 0.05) after caffeine than after placebo. CONCLUSION: Caffeine impaired insulin sensitivity in women with GDM. Additional research regarding more specific dietary caffeine recommendations for women with GDM is warranted.

Rapid exercise-induced changes in PGC-1alpha mRNA and protein in human skeletal muscle.

The mRNA of the nuclear coactivator peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) increases during prolonged exercise and is influenced by carbohydrate availability. It is unknown if the increases in mRNA reflect the PGC-1alpha protein or if glycogen stores are an important regulator. Seven male subjects [23 +/- 1.3 yr old, maximum oxygen uptake (Vo(2 max)) 48.4 +/- 0.8 ml.kg(-1).min(-1)] exercised to exhaustion ( approximately 2 h) at 65% Vo(2 max) followed by ingestion of either a high-carbohydrate (HC) or low-carbohydrate (LC) diet (7 or 2.9 g.kg(-1).day(-1), respectively) for 52 h of recovery. Glycogen remained depressed in LC (P < 0.05) while returning to resting levels by 24 h in HC. PGC-1alpha mRNA increased both at exhaustion (3-fold) and 2 h later (6.2-fold) (P < 0.05) but returned to rest levels by 24 h. PGC-1alpha protein increased (P < 0.05) 23% at exhaustion and remained elevated for at least 24 h (P < 0.05). While there was no direct treatment effect (HC vs. LC) for PGC-1alpha mRNA or protein, there was a linear relationship between the changes in glycogen and those in PGC-1alpha protein during exercise and recovery (r = -0.68, P < 0.05). In contrast, PGC-1beta did not increase with exercise but rather decreased (P < 0.05) below rest level at 24 and 52 h, and the decrease was greater (P < 0.05) in LC. PGC-1alpha protein content increased in prolonged exercise and remained upregulated for 24 h, but this could not have been predicted by the changes in mRNA. The beta-isoform declined rather than increasing, and this was greater when glycogen was not resynthesized to rest levels.

An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus.

Obesity and type 2 diabetes mellitus (T2DM) have been associated with a state of chronic low-grade inflammation. We examined the effect of exercise without weight loss on circulating inflammatory biomarkers in previously sedentary lean men and obese men with and without T2DM. Middle-aged men (8 lean, 8 obese, and 8 obese with T2DM) performed 60 minutes of aerobic exercise 5 times per week for 12 weeks without a reduction in body weight. Subjects underwent a hyperinsulinemic-euglycemic clamp before and after the 12-week exercise program to assess insulin sensitivity. Circulating interleukin-6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein concentrations were measured by sandwich enzyme-linked immunosorbent assay before and after the exercise intervention. Body fat was measured using magnetic resonance imaging, and waist circumference was recorded for each subject pre- and postexercise intervention. Waist circumference and plasma IL-6 concentrations were significantly lower (P < .05) after exercise training despite no change in body weight or insulin sensitivity. There were no correlations between insulin sensitivity and IL-6. Fasting plasma PAI-1 concentration was significantly lower in the lean group compared with the obese group both pre- and postexercise intervention (P < .05). There were no changes in C-reactive protein or PAI-1 concentrations after exercise training. A 12-week exercise intervention led to reductions in waist circumference and fasting IL-6 concentrations in previously sedentary lean and obese men with or without T2DM, demonstrating significant changes in clinically relevant diabetes-related parameters despite no change in body weight.

Inverse relationship between PGC-1alpha protein expression and triacylglycerol accumulation in rodent skeletal muscle.

PGC-1alpha is a key regulator of tissue metabolism, including skeletal muscle. Because it has been shown that PGC-1alpha alters the capacity for lipid metabolism, it is possible that PGC-1alpha expression is regulated by the intramuscular lipid milieu. Therefore, we have examined the relationship between PGC-1alpha protein expression and the intramuscular fatty acid accumulation in hindlimb muscles of animals in which the capacity for fatty acid accumulation in muscle is increased (Zucker obese rat) or reduced [FAT/CD36 null (KO) mice]. Rates of palmitate incorporation into triacylglycerols were determined in perfused red (RG) and white gastrocnemius (WG) muscles of lean and obese Zucker rats and in perfused RG and WG muscles of FAT/CD36 KO and wild-type (WT) mice. In obese Zucker rats, the rate of palmitate incorporation into triacylglycerol depots in RG and WG muscles were 28 and 24% greater than in lean rats (P < 0.05). In FAT/CD36 KO mice, the rates of palmitate incorporation into triacylglycerol depots were lower in RG (-50%) and WG muscle (-24%) compared with the respective muscles in WT mice (P < 0.05). In the obese animals, PGC-1alpha protein content was reduced in both RG (-13%) and WG muscles (-15%) (P < 0.05). In FAT/CD36 KO mice, PGC-1alpha protein content was upregulated in both RG (+32%, P < 0.05) and WG muscles (+50%, P < 0.05). In conclusion, from studies in these two animal models, it appears that PGC-1alpha protein expression is inversely related to components of intramuscular lipid metabolism, because 1) PGC-1alpha protein expression is downregulated when triacylglycerol synthesis rates, an index of intramuscular lipid metabolism, are increased, and 2) PGC-1alpha protein expression is upregulated when triacylglycerol synthesis rates are reduced. Therefore, we speculate that the intramuscular lipid sensing may be involved in regulating the protein expression of PGC-1alpha in skeletal muscle.

Caffeine ingestion is associated with reductions in glucose uptake independent of obesity and type 2 diabetes before and after exercise training.

OBJECTIVE: We investigated the effect of caffeine ingestion on insulin sensitivity in sedentary lean men (n = 8) and obese men with (n = 7) and without (n = 8) type 2 diabetes. We also examined whether chronic exercise influences the relationship between caffeine and insulin sensitivity in these individuals. RESEARCH DESIGN AND METHODS: Subjects underwent two hyperinsulinemic-euglycemic clamp procedures, caffeine (5 mg/kg body wt) and placebo, in a double-blind, randomized manner before and after a 3-month aerobic exercise program. Body composition was measured by magnetic resonance imaging. RESULTS: At baseline, caffeine ingestion was associated with a significant reduction (P < 0.05) in insulin sensitivity by a similar magnitude in the lean (33%), obese (33%), and type 2 diabetic (37%) groups in comparison with placebo. After exercise training, caffeine ingestion was still associated with a reduction (P < 0.05) in insulin sensitivity by a similar magnitude in the lean (23%), obese (26%), and type 2 diabetic (36%) groups in comparison with placebo. Exercise was not associated with a significant increase in insulin sensitivity in either the caffeine or placebo trials, independent of group (P > 0.10). CONCLUSIONS: Caffeine consumption is associated with a substantial reduction in insulin-mediated glucose uptake independent of obesity, type 2 diabetes, and chronic exercise.

Nutra-ergonomics: influence of nutrition on physical employment standards and the health of workers.

The importance of ergonomics across several scientific domains, including biomechanics, psychology, sociology, and physiology, have been extensively explored. However, the role of other factors that may influence the health and productivity of workers, such as nutrition, is generally overlooked. Nutra-ergonomics describes the interface between workers, their work environment, and performance in relation to their nutritional status. It considers nutrition to be an integral part of a safe and productive workplace that encompasses physical and mental health as well as the long-term wellbeing of workers. This review explores the knowledge, awareness, and common practices of nutrition, hydration, stimulants, and fortified product use employed prior to physical employment standards testing and within the workplace. The influence of these nutra-ergonomic strategies on physical employment standards, worker safety, and performance will be examined. Further, the roles, responsibilities, and implications for the applicant, worker, and the employer will be discussed within the context of nutra-ergonomics, with reference to the provision and sustainability of an environment conducive to optimize worker health and wellbeing. Beyond physical employment standards, workplace productivity, and performance, the influence of extended or chronic desynchronization (irregular or shift work) in the work schedule on metabolism and long-term health, including risk of developing chronic and complex diseases, is discussed. Finally, practical nutra-ergonomic strategies and recommendations for the applicant, worker, and employer alike will be provided to enhance the short- and long-term safety, performance, health, and wellbeing of workers.

Towards best practice in physical and physiological employment standards.

While the scope of the term physical employment standards is wide, the principal focus of this paper is on standards related to physiological evaluation of readiness for work. Common applications of such employment standards for work are in public safety and emergency response occupations (e.g., police, firefighting, military), and there is an ever-present need to maximize the scientific quality of this research. Historically, most of these occupations are male-dominated, which leads to potential sex bias during physical demands analysis and determining performance thresholds. It is often assumed that older workers advance to positions with lower physical demand. However, this is not always true, which raises concerns about the long-term maintenance of physiological readiness. Traditionally, little attention has been paid to the inevitable margin of uncertainty that exists around cut-scores. Establishing confidence intervals around the cut-score can reduce for this uncertainty. It may also be necessary to consider the effects of practise and biological variability on test scores. Most tests of readiness for work are conducted under near perfect conditions, while many emergency responses take place under far more demanding and unpredictable conditions. The potential impact of protective clothing, respiratory protection, load carriage, environmental conditions, nutrition, fatigue, sensory deprivation, and stress should also be considered when evaluating readiness for work. In this paper, we seek to establish uniformity in terminology in this field, identify key areas of concern, provide recommendations to improve both scientific and professional practice, and identify priorities for future research.

17beta-estradiol supplementation decreases glucose rate of appearance and disappearance with no effect on glycogen utilization during moderate intensity exercise in men.

CONTEXT AND OBJECTIVE: Women use less carbohydrate during endurance exercise, as compared with men. In rodents, 17beta-estradiol (E2) supplementation robustly increases lipid use and lowers muscle and liver glycogen use during exercise. E2 supplementation has been found to influence substrate selection by decreasing glucose rate of appearance (Ra), disappearance (Rd), and metabolic clearance rate during exercise in humans; however, neither a change in total carbohydrate use nor a sparing of muscle glycogen was demonstrated. SUBJECTS AND METHODS: We investigated the effect of 8 d of E2 (2 mg/d) supplementation on glucose turnover and net muscle glycogen use in 11 men using a randomized, double-blind, placebo-controlled, crossover design. Subjects underwent primed constant infusion of [6,6-(2)H]glucose, and muscle biopsies were taken before and after 90 min of cycling at 65% maximal oxygen uptake. RESULTS: E2 supplementation decreased the respiratory exchange ratio (P = 0.03) and glucose Ra and Rd (both P = 0.04) during exercise, as compared with placebo. E2 supplementation lowered proglycogen (P < 0.05) and total glycogen (P = 0.04) concentration, as compared with placebo; however, there was no effect of E2 on net muscle glycogen use during exercise. CONCLUSIONS: These findings show that E2 supplementation alters fuel selection in exercising men by increasing lipid use and reducing carbohydrate use, glucose Ra (primarily liver glucose production), and Rd (primarily muscle glucose uptake). Furthermore, E2 reduces the basal level of total muscle glycogen, particularly the proglycogen form.

Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise.

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.

Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without Type 2 diabetes.

It is unclear whether chronic exercise without caloric restriction or weight loss is a useful strategy for obesity reduction in obese men with and without Type 2 diabetes (T2D). We examined the effects of exercise without weight loss on total and regional adiposity and skeletal muscle mass and composition in lean men and in obese men with and without T2D. Twenty-four men participated in 13 wk of supervised aerobic exercise, five times per week for 60 min at a moderate intensity (approximately 60% peak oxygen uptake). Total and regional body composition was measured by magnetic resonance imaging. Skeletal muscle composition was determined using computed tomography. Cardiorespiratory fitness was assessed using a graded maximal treadmill test. Body weight did not change within any group in response to exercise (P > 0.1). Significant reductions in total, abdominal subcutaneous, and visceral fat were observed within each group (P < 0.01). The reduction in total and abdominal subcutaneous fat was not different (P > 0.1) between groups; however, the reduction in visceral fat was greater (P < 0.01) in the obese and T2D groups by comparison to the lean group. A significant (P < 0.01) increase in total skeletal muscle, high-density muscle area, and mean muscle attenuation was observed independent of group, and these changes were not different between groups (P > 0.1). Accordingly, whole body fat-to-muscle ratio was increased (P < 0.01) independent of groups. In conclusion, regular exercise without weight loss is associated with a substantial reduction in total and visceral fat and in skeletal muscle lipid in both obesity and T2D.

Glycogenin activity and mRNA expression in response to volitional exhaustion in human skeletal muscle.

Glycogenolysis results in the selective catabolism of individual glycogen granules by glycogen phosphorylase. However, once the carbohydrate portion of the granule is metabolized, the fate of glycogenin, the protein primer of granule formation, is not known. To examine this, male subjects (n = 6) exercised to volitional exhaustion (Exh) on a cycle ergometer at 75% maximal O2 uptake. Muscle biopsies were obtained at rest, 30 min, and Exh (99 +/- 10 min). At rest, total glycogen concentration was 497 +/- 41 and declined to 378 +/- 51 mmol glucosyl units/kg dry wt following 30 min of exercise (P < 0.05). There were no significant changes in proglycogen, macroglycogen, glycogenin activity, or mRNA in this period (P > or = 0.05). Exh resulted in decreases in total glycogen, proglycogen, and macroglycogen as well as glycogenin activity (P < 0.05). These decrements were associated with a 1.9 +/- 0.4-fold increase in glycogenin mRNA over resting values (P < 0.05). Glycogenolysis in the initial exercise period (0-30 min) was not adequate to induce changes in glycogenin; however, later in exercise when concentration and granule number decreased further, decrements in glycogenin activity and increases in glycogenin mRNA were demonstrated. Results show that glycogenin becomes inactivated with glycogen catabolism and that this event coincides with an increase in glycogenin gene expression as exercise and glycogenolysis progress.

Caffeine ingestion increases the insulin response to an oral-glucose-tolerance test in obese men before and after weight loss.

BACKGROUND: Caffeine ingestion decreases the insulin sensitivity index (ISI) for an oral-glucose-tolerance test (OGTT) and decreases insulin-induced glucose disposal in lean male subjects during a hyperinsulinemic clamp. OBJECTIVE: We examined the effects of caffeine ingestion on insulin and glucose homeostasis in obese men before and after a nutrition and exercise intervention. DESIGN: Nine sedentary, obese [body mass index (in kg/m(2)): 34.0 +/- 1.0] men who had refrained from exercise and caffeine ingestion for 48 h underwent 2 oral-glucose-tolerance tests (OGTTs). The subjects randomly received caffeine (5 mg/kg) or placebo 1 h before each OGTT. After a 12-wk nutrition and exercise intervention, during which time the subjects avoided dietary caffeine, the OGTTs were repeated. RESULTS: The intervention resulted in decreases (P < or = 0.05) in body weight (8.5 +/- 1.5 kg), percentage body fat (2.8 +/- 0.7%), and fasting glucose, insulin, and proinsulin concentrations and increases in the ISI for the placebo OGTT (P < or = 0.05). Caffeine caused a greater (P < or = 0.05) OGTT insulin response and a lower (P < or = 0.05) ISI both before and after weight loss. The proinsulin-insulin ratio indicated that neither weight loss nor caffeine affected the nature of the beta cell secretion of insulin. CONCLUSIONS: A nutrition and exercise intervention improved, whereas caffeine ingestion impaired, insulin-glucose homeostasis in obese men. The results are consistent with previous findings that caffeine ingestion contributes to insulin resistance.

Glutamate ingestion and its effects at rest and during exercise in humans.

Glutamate is central to several transamination reactions that affect the production of ammonia, alanine, glutamine, as well as TCA cycle intermediates during exercise. To further study glutamate metabolism, we administered 150 mg/kg body wt of monosodium glutamate (MSG) and placebo to seven male subjects who then either rested or exercised (15-min cycling at approximately 85% maximal oxygen consumption). MSG ingestion resulted in elevated plasma glutamate, aspartate, and taurine, both at rest and during exercise (P < 0.05), whereas most other amino acids were unchanged. Neither plasma alanine nor ammonia was altered at rest. During exercise and after glutamate ingestion, alanine was increased (P < 0.05) and ammonia was attenuated (P < 0.05). Glutamine was also elevated after glutamate ingestion during rest and exercise trials. MSG administration also resulted in elevated insulin levels (P < 0.05), which were parallel to the trend in C-peptide levels. Thus MSG can successfully elevate plasma glutamate, both at rest and during exercise. The plasma amino acid responses suggest that increased glutamate availability during exercise alters its distribution in transamination reactions within active muscle, which results in elevated alanine and decreased ammonia levels.

Caffeine-induced impairment of glucose tolerance is abolished by beta-adrenergic receptor blockade in humans.

The caffeine-induced impairment of insulin action is commonly attributed to adenosine receptor (AR) antagonism in skeletal muscle. However, epinephrine, a potent inhibitor of insulin actions, is increased after caffeine ingestion. We tested the hypothesis that the insulin antagonistic effects of caffeine are mediated by epinephrine, and not by AR antagonism, in seven healthy men. On four separate occasions, they received 1) dextrose (placebo, PL), 2) 5 mg/kg caffeine (CAF), 3) 80 mg of propranolol (PR), and 4) 5 mg/kg caffeine + 80 mg of propranolol (CAF + PR) before an oral glucose tolerance test (OGTT). Blood glucose was similar among trials before and during the OGTT. Plasma epinephrine was elevated (P < 0.05) in CAF and CAF + PR. Areas under the insulin and C-peptide curves were 42 and 39% greater (P < 0.05), respectively, in CAF than in PL, PR, and CAF + PR. In the presence of propranolol (CAF + PR), these responses were similar to PL and PR. These data suggest that the insulin antagonistic effects of caffeine in vivo are mediated by elevated epinephrine rather than by peripheral AR antagonism.

Effect of exercise on FA profiles in n-3 FA-supplemented and -nonsupplemented premenopausal women.

The purpose of this double-blind study was to investigate the influence of exercise on the FA profile of the non-esterified FA (NEFA) and phospholipid fractions in plasma of sedentary women supplemented with n-3 FA vs. women supplemented with oil containing no n-3 FA. Twenty sedentary, premenopausal women were randomly assigned to receive 12 capsules daily of either fish oil (3.5 g EPA and 2.4 g DHA per day, each as the ethyl ester) or evening primrose oil capsules (no detectable EPA or DHA). Each subject consumed the capsules for one menstrual cycle. At the end of the supplementation period, the sedentary subjects underwent an acute exercise trial [55% maximal oxygen consumption (VO2 max), 45 min] on a cycle ergometer. Two subjects in the fish oil group were removed from all calculations owing to noncompliance for reasons not related to side effects. There were no changes in the phospholipid composition of either group of women after exercise. In both control and fish oil-supplemented women, NEFA levels in general rose after exercise. There were no changes in the percentage of any given individual NEFA in either supplementation group. However, absolute levels of certain individual NEFA (16:0, 18:0, 18:1, and 18:3n-3) increased with exercise. Women supplemented with fish oil had increased levels of n-3 NEFA IEPA, DHA, and docosapentaenoic acid (DPA)] prior to exercise. Exercise did not, however, increase the absolute levels of n-3 NEFA in the blood.