The effect of creatine supplementation on glucose uptake in rat skeletal muscle

Glucose transport in muscle is a function of the muscle metabolic state, as evidenced by the increase in glucose transport which occurs with conditions of altered aerobic metabolism such as hypoxia or contractile activity. The energy state of the muscle can be determined by the muscle phosphocreatine concentration. Dietary supplementation of creatine has been shown to increase both phosphocreatine (PCr) and creatine (TCr) levels in muscle, although not in the same proportion, so that the PCr/TCr ratio falls suggesting an altered energy state in the cell. The purpose of this study was to determine the effect of increased creatine content on glucose uptake in muscle. PCr and TCr were determined in plantaris muscles from rats following five weeks of dietary supplementation of creatine monohydrate (300 mg/kg/day). (3)H-2-deoxyglucose uptake was measured in epitrochlearis muscles incubated in the presence or absence of a maximally stimulating dose of insulin. Despite a significant increase in creatine content in muscle, neither basal nor insulin-stimulated glucose uptake was altered in creatine supplemented rats. Since PCr levels were not increased with creatine supplementation, these results suggest that the actual concentration of PCr is a more important determinant of glucose uptake than the PCr/TCr ratio.     

Effects of repeated creatine supplementation on muscle, plasma, and urine creatine levels

The purpose of this case study was to examine the effects of repeated creatine administration on muscle phosphocreatine, plasma creatine, and urine creatine. One male subject (age, 32 years; body mass, 78.4 kg; height, 160 cm; resistance training experience, 15 years) ingested creatine (20 g.d(-1) for 5 days) during 2 bouts separated by a 30-day washout period. Muscle phosphocreatine was measured before and after supplementation. On day 1 of supplementation, blood samples were taken immediately before and hourly for 5 hours following ingestion of 5 g of creatine, and a pharmacokinetic analysis of plasma creatine was conducted. Twenty-four-hour urine collections were conducted before and for 5 days during supplementation. Muscle phosphocreatine increased 45% following the first supplementation bout, decreased 22% during the 30-day washout period, and increased 25% following the second bout. There were no meaningful differences in plasma creatine pharmacokinetic parameters between bouts 1 and 2. Total urine creatine losses during supplementation were 63.2 and 63.4 g during bouts 1 and 2, respectively. The major findings were that (a) a 30-day washout period is insufficient time for muscle phosphocreatine to return to baseline following creatine supplementation but is sufficient time for plasma and urine creatine levels to return to presupplementation values; (b) postsupplementation muscle phosphocreatine levels were similar following bouts 1 and 2 despite 23% higher presupplementation muscle phosphocreatine before bout 2; and (c) the increased muscle phosphocreatine that persisted throughout the 30-day washout period corresponded with maintenance of increased body mass (+2.0 kg). Athletes should be aware that the washout period for muscle creatine to return to baseline levels may be longer than 30 days in some individuals, and this may be accompanied by a persistent increase in body mass.     

Creatine supplementation attenuates corticosteroid-induced muscle wasting and impairment of exercise performance in rats.

The objective of the present study was to investigate whether creatine (Cr) could attenuate the deleterious effects of high doses of dexamethasone (Dexa) on body mass, exercise performance, and respiratory variables of rodents. Forty-four Wistar rats performed incremental maximal exercise tests. They were then assigned to four groups: G1: subcutaneous (s.c.) and intraperitoneal (i.p.) saline; G2: s.c. saline and i.p. Cr (250 mg x kg(-1) x day(-1)); G3: s.c. Dexa (7.5 mg x kg(-1) x day(-1)) and i.p. saline; G4: s.c. Dexa and i.p. Cr. New exercise tests and analysis of the respiratory pattern under resting conditions and after stimulation with doxapram (2 mg/kg i.p.) were performed after 18 days. Post- minus pretreatment differences were compared between groups. G3 and G4 showed a significant impairment in body mass gain compared with G1 and G2 (P < 0.05) (G1: 65.3 +/- 26.1, G2: 93.1 +/- 27.4, G3: -18.4 +/- 20.1, G4: 9.8 +/- 23.1 kg x 10(-3)). Similar results were observed for maximal oxygen consumption (G1: 9.5 +/- 8.5, G2: 25.8 +/- 14.5, G3: -25.5 +/- 6.0, G4: -4.8 +/- 9.5 ml x kg(-1) x min(-1)) and test duration (G1: 43.0 +/- 45.0, G2: 72.0 +/- 59.5, G3: -165.0 +/- 60.6, G4: -48.0 +/- 48.5 s). Simultaneous use of Cr significantly attenuated the Dexa-induced impairment of the last two variables. Cr attenuated Dexa-induced gastrocnemius and diaphragm muscle weight losses and the atrophy of gastrocnemius type IIb fibers. Cr supplementation had only small effects on Dexa-induced respiratory changes. These results suggest that Cr may play a role in the prophylaxis or treatment of steroid-induced myopathy.     

Effects of creatine supplementation and resistance training on muscle strength and weightlifting performance

Creatine monohydrate has become the supplement of choice for many athletes striving to improve sports performance. Recent data indicate that athletes may not be using creatine as a sports performance booster per se but instead use creatine chronically as a training aid to augment intense resistance training workouts. Although several studies have evaluated the combined effects of creatine supplementation and resistance training on muscle strength and weightlifting performance, these data have not been analyzed collectively. The purpose of this review is to evaluate the effects of creatine supplementation on muscle strength and weightlifting performance when ingested concomitant with resistance training. The effects of gender, interindividual variability, training status, and possible mechanisms of action are discussed. Of the 22 studies reviewed, the average increase in muscle strength (1, 3, or 10 repetition maximum [RM]) following creatine supplementation plus resistance training was 8% greater than the average increase in muscle strength following placebo ingestion during resistance training (20 vs. 12%). Similarly, the average increase in weightlifting performance (maximal repetitions at a given percent of maximal strength) following creatine supplementation plus resistance training was 14% greater than the average increase in weightlifting performance following placebo ingestion during resistance training (26 vs. 12%). The increase in bench press 1RM ranged from 3 to 45%, and the improvement in weightlifting performance in the bench press ranged from 16 to 43%. Thus there is substantial evidence to indicate that creatine supplementation during resistance training is more effective at increasing muscle strength and weightlifting performance than resistance training alone, although the response is highly variable.     

Effects of chronic sleep deprivation on glucose homeostasis in rats

Sleep and Biological Rhythms - Epidemiological studies have shown that chronic sleep disturbances resulted in metabolic disorders. The purpose of this study was to assess the relationship between...     

Effects of glucose supplementation on gastric emptying, blood glucose homeostasis, and appetite in the elderly

The aims of this study were to evaluate the effects of dietary glucose supplementation on gastric emptying (GE) of both glucose and fat, postprandial blood glucose homeostasis, and appetite in eight older subjects (4 males, 4 females, aged 65--84 yr). GE of a drink (15 ml olive oil and 33 g glucose dissolved in 185 ml water), blood glucose, insulin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), and appetite (diet diaries, visual analog scales, and food intake at a buffet meal consumed after the GE study) were evaluated twice, after 10 days on a standard or a glucose-supplemented diet (70 g glucose 3 times a day). Glucose supplementation accelerated GE of glucose (P < 0.05), but not oil; there was a trend for an increase in GIP (at 15 min, P = 0.06), no change in GLP-1, an earlier insulin peak (P < 0.01), and a subsequent reduction in blood glucose (at 75 min, P < 0.01). Glucose supplementation had no effect on food intake during each diet so that energy intake was greater (P < 0.001) during the glucose-supplemented diet. Appetite ratings and energy intake at the buffet meal were not different. We conclude that, in older subjects, glucose supplementation 1) accelerates GE of glucose, but not fat; 2) modifies postprandial blood glucose homeostasis; and 3) increases energy intake.     

Changes in UPR-PERK pathway and muscle hypertrophy following resistance training and creatine supplementation in rats

Journal of Physiology and Biochemistry - The unfolded protein response (UPR) plays a pivotal role in some exercise training–induced physiological adaptation. Our aim was to evaluate the...     

Taurine supplementation modulates glucose homeostasis and islet function

Taurine is a conditionally essential amino acid for human that is involved in the control of glucose homeostasis; however, the mechanisms by which the amino acid affects blood glucose levels are unknown. Using an animal model, we have studied these mechanisms. Mice were supplemented with taurine for 30 d. Blood glucose homeostasis was assessed by intraperitoneal glucose tolerance tests (IPGTT). Islet cell function was determined by insulin secretion, cytosolic Ca2+ measurements and glucose metabolism from isolated islets. Islet cell gene expression and translocation was examined via immunohistochemistry and quantitative real-time polymerase chain reaction. Insulin signaling was studied by Western blot. Islets from taurine-supplemented mice had: (i) significantly higher insulin content, (ii) increased insulin secretion at stimulatory glucose concentrations, (iii) significantly displaced the dose-response curve for glucose-induced insulin release to the left, (iv) increased glucose metabolism at 5.6 and 11.1-mmol/L concentrations; (v) slowed cytosolic Ca2+ concentration ([Ca2+]i) oscillations in response to stimulatory glucose concentrations; (vi) increased insulin, sulfonylurea receptor-1, glucokinase, Glut-2, proconvertase and pancreas duodenum homeobox-1 (PDX-1) gene expression and (vii) increased PDX-1 expression in the nucleus. Moreover, taurine supplementation significantly increased both basal and insulin stimulated tyrosine phosphorylation of the insulin receptor in skeletal muscle and liver tissues. Finally, taurine supplemented mice showed an improved IPGTT. These results indicate that taurine controls glucose homeostasis by regulating the expression of genes required for glucose-stimulated insulin secretion. In addition, taurine enhances peripheral insulin sensitivity.     

Effects of creatine supplementation on glucose tolerance and insulin sensitivity in sedentary healthy males undergoing aerobic training

Recent findings have indicated that creatine supplementation may affect glucose metabolism. This study aimed to examine the effects of creatine supplementation, combined with aerobic training, on glucose tolerance in sedentary healthy male. Subjects (n = 22) were randomly divided in two groups and were allocated to receive treatment with either creatine (CT) ( approximately 10 g . day over three months) or placebo (PT) (dextrose). Administration of treatments was double blind. Both groups underwent moderate aerobic training. An oral glucose tolerance test (OGTT) was performed and both fasting plasma insulin and the homeostasis model assessment (HOMA) index were assessed at the start, and after four, eight and twelve weeks. CT demonstrated significant decrease in OGTT area under the curve compared to PT (P = 0.034). There were no differences between groups or over time in fasting insulin or HOMA. The results suggest that creatine supplementation, combined with aerobic training, can improve glucose tolerance but does not affect insulin sensitivity, and may warrant further investigation with diabetic subjects.     

Effect of creatine supplementation on sprint exercise performance and muscle metabolism

The aim of thepresent study was to examine the effect of creatine supplementation(CrS) on sprint exercise performance and skeletal muscle anaerobicmetabolism during and after sprint exercise. Eight active, untrainedmen performed a 20-s maximal sprint on an air-braked cycle ergometerafter 5 days of CrS [30 g creatine (Cr) + 30 g dextrose perday] or placebo (30 g dextrose per day). The trials wereseparated by 4 wk, and a double-blind crossover design was used. Muscleand blood samples were obtained at rest, immediately after exercise,and after 2 min of passive recovery. CrS increased the muscle total Crcontent (9.5 ± 2.0%, P < 0.05, mean ± SE); however, 20-s sprint performance was not improved byCrS. Similarly, the magnitude of the degradation or accumulation ofmuscle (e.g., adenine nucleotides, phosphocreatine, inosine 5'-monophosphate, lactate, and glycogen) and plasma metabolites (e.g., lactate, hypoxanthine, and ammonia/ammonium) were also unaffected by CrS during exercise or recovery. These data demonstrated that CrS increased muscle total Cr content, but the increase did notinduce an improved sprint exercise performance or alterations inanaerobic muscle metabolism.

     

Combined creatine and protein supplementation in conjunction with resistance training promotes muscle GLUT-4 content and glucose tolerance in humans.

The present study was undertaken to explore the effects of creatine and creatine plus protein supplementation on GLUT-4 and glycogen content of human skeletal muscle. This was investigated in muscles undergoing a decrease (immobilization) and subsequent increase (resistance training) in activity level, compared with muscles with unaltered activity pattern. A double-blind, placebo-controlled trial was performed by 33 young healthy subjects. The subjects' right legs were immobilized with a cast for 2 wk, followed by a 6-wk resistance training program for the right knee extensor muscles. The participants were supplemented throughout the study with either placebo (Pl group) or creatine (Cr group) or with creatine during immobilization and creatine plus protein during retraining (Cr+P group). Needle biopsies were bilaterally taken from the vastus lateralis. GLUT-4 protein expression was reduced by the immobilization in all groups (P < 0.05). During retraining, GLUT-4 content increased (P < 0.05) in both Cr (+24%) and Cr+P (+33%), which resulted in higher posttraining GLUT-4 expression compared with Pl (P < 0.05). Compared with Pl, muscle glycogen content was higher (P < 0.05) in the trained leg in both Cr and Cr+P. Supplements had no effect on GLUT-4 expression or glycogen content in contralateral control legs. Area under the glucose curve during the oral glucose tolerance test was decreased from 232 +/- 23 mmol. l(-1). min(-1) at baseline to 170 +/- 23 mmol. l(-1). min(-1) at the end of the retraining period in Cr+P (P < 0.05), but it did not change in Cr or Pl. We conclude that creatine intake stimulates GLUT-4 and glycogen content in human muscle only when combined with changes in habitual activity level. Furthermore, combined protein and creatine supplementation improved oral glucose tolerance, which is supposedly unrelated to the changes in muscle GLUT-4 expression.     

Effects of resistance exercise with and without creatine supplementation on gene expression and cell signaling in human skeletal muscle.

To test the hypothesis that creatine supplementation would enhance the anabolic responses of muscle cell signaling and gene expression to exercise, we studied nine subjects who received either creatine or a placebo (maltodextrin) for 5 days in a double-blind fashion before undergoing muscle biopsies: at rest, immediately after exercise (10 x 10 repetitions of one-leg extension at 80% 1 repetition maximum), and 24 and 72 h later (all in the morning after fasting overnight). Creatine supplementation decreased the phosphorylation state of protein kinase B (PKB) on Thr308 at rest by 60% (P < 0.05) and that of eukaryotic initiation factor 4E-binding protein on Thr37/46 (4E-BP1) by 30% 24 h postexercise (P < 0.05). Creatine increased mRNA for collagen 1 (alpha(1)), glucose transporter-4 (GLUT-4), and myosin heavy chain I at rest by 250%, 45%, and 80%, respectively, and myosin heavy chain IIA (MHCIIA) mRNA immediately after exercise by 70% (all P < 0.05). Immediately after exercise, and independent of creatine, mRNA for muscle atrophy F-box (MAFbx), MHCIIA, peroxisome proliferator-activated receptor gamma coactivator-1alpha, and interleukin-6 were upregulated (60-350%; P < 0.05); the phosphorylation state of p38 both in the sarcoplasm and nucleus were increased (12- and 25-fold, respectively; both P < 0.05). Concurrently, the phosphorylation states of PKB (Thr308) and 4E-BP1 (Thr37/46) were decreased by 50% and 75%, respectively (P < 0.05). Twenty-four hours postexercise, MAFbx, myostatin, and GLUT-4 mRNA expression decreased below preexercise values (-35 to -50%; P < 0.05); calpain 1 mRNA increased 70% 72 h postexercise (P < 0.05) and at no other time. In conclusion, 5 days of creatine supplementation do not enhance anabolic signaling but increase the expression of certain targeted genes.     

Effects of creatine supplementation on performance and training adaptations

Creatine has become a popular nutritional supplement among athletes. Recent research has also suggested that there may be a number of potential therapeutic uses of creatine. This paper reviews the available research that has examined the potential ergogenic value of creatine supplementation on exercise performance and training adaptations. Review of the literature indicates that over 500 research studies have evaluated the effects of creatine supplementation on muscle physiology and/or exercise capacity in healthy, trained, and various diseased populations. Short-term creatine supplementation (e.g. 20 g/day for 5–7 days) has typically been reported to increase total creatine content by 10–30% and phosphocreatine stores by 10–40%. Of the approximately 300 studies that have evaluated the potential ergogenic value of creatine supplementation, about 70% of these studies report statistically significant results while remaining studies generally report non-significant gains in performance. No study reports a statistically significant ergolytic effect. For example, short-term creatine supplementation has been reported to improve maximal power/strength (5–15%), work performed during sets of maximal effort muscle contractions (5–15%), single-effort sprint performance (1–5%), and work performed during repetitive sprint performance (5–15%). Moreover, creatine supplementation during training has been reported to promote significantly greater gains in strength, fat free mass, and performance primarily of high intensity exercise tasks. Although not all studies report significant results, the preponderance of scientific evidence indicates that creatine supplementation appears to be a generally effective nutritional ergogenic aid for a variety of exercise tasks in a number of athletic and clinical populations.     

Impact of glutamine supplementation on glucose homeostasis during and after exercise.

The interaction of glutamine availability and glucose homeostasis during and after exercise was investigated, measuring whole body glucose kinetics with [3-3H]glucose and net organ balances of glucose and amino acids (AA) during basal, exercise, and postexercise hyperinsulinemic-euglycemic clamp periods in six multicatheterized dogs. Dogs were studied twice in random treatment order: once with glutamine (12 micromol.kg(-1).min(-1); Gln) and once with saline (Con) infused intravenously during and after exercise. Plasma glucose fell by 7 mg/dl with exercise in Con (P < 0.05), but it did not fall with Gln. Gln further stimulated whole body glucose production and utilization an additional 24% above a normal exercise response (P < 0.05). Net hepatic uptake of glutamine and alanine was greater with Gln than Con during exercise (P < 0.05). Net hepatic glucose output was increased sevenfold during exercise with Gln (P < 0.05) but not with Con. Net hindlimb glucose uptake was increased similarly during exercise in both groups (P < 0.05). During the postexercise hyperinsulinemic-euglycemic period, glucose production decreased to near zero with Con, but it did not decrease below basal levels with Gln. Gln increased glucose utilization by 16% compared with Con after exercise (P < 0.05). Furthermore, net hindlimb glucose uptake in the postexercise period was increased approximately twofold vs. basal with Gln (P < 0.05) but not with Con. Net hepatic uptake of glutamine during the postexercise period was threefold greater for Gln than Con (P < 0.05). In conclusion, glutamine availability modulates glucose homeostasis during and after exercise, which may have implications for postexercise recovery.     

The effect of creatine supplementation on mass and performance of rat skeletal muscle

This study investigated the effect of dietary creatine supplementation on hypertrophy and performance of rat skeletal muscle. Male Sprague-Dawley rats underwent either tibialis anterior ablation or partial ablation of the plantaris/gastrocnemius to induce compensatory hypertrophy of the extensor digitorum longus (EDL) or soleus respectively, or sham surgery. Creatine (300 mg/kg) was administered to one half of each group for 5 weeks, after which force production was measured. With the leg fixed at the knee and ankle, the distal tendon of the EDL or soleus was attached to a force transducer and the muscle was electrically stimulated via the sciatic nerve. Synergist ablation resulted in a significant increase in EDL mass and in soleus mass relative to control muscles. However, no effect of creatine supplementation on muscle mass or performance was found between control and either group of creatine-treated rats. Despite an apparent increase in muscle creatine content, creatine supplementation did not augment muscle hypertrophy or force production in rat EDL or soleus muscle, providing evidence that the potential benefits of creatine supplementation are not due to a direct effect on muscle but rather to an enhanced ability to train.     

Effects of creatine supplementation on the energy cost of muscle contraction: a 31P-MRS study.

Five women and 3 men (29.8 +/- 1.4 yr) performed dynamic knee-extension exercise inside a magnetic resonance system (means +/- SE). Two trials were performed 7-14 days apart, consisting of a 4- to 5-min exhaustive exercise bout. To determine quadriceps cost of contraction, brief static and dynamic contractions were performed pre- and postexercise. (31)P spectra were used to determine pH and relative concentrations of P(i), phosphocreatine (PCr), and betaATP. Subjects consumed 0.3 g. kg(-1). day(-1) of a placebo (trial 1) or creatine (trial 2) for 5 days before each trial. After creatine supplementation, resting DeltaPCr increased from 40.7 +/- 1.8 to 46. 6 +/- 1.1 mmol/kg (P = 0.04) and PCr during exercise declined from -29.6 +/- 2.4 to -34.1 +/- 2.8 mmol/kg (P = 0.02). Muscle static (DeltaATP/N) and dynamic (DeltaATP/J) costs of contraction were unaffected by creatine supplementation as well as were ATP, P(i), pH, PCr resynthesis rate, and muscle strength and endurance. DeltaATP/J and DeltaATP/N were greatest at the onset of the exercise protocol (P < 0.01). In summary, creatine supplementation increased muscle PCr concentration, which did not affect muscle ATP cost of contraction.     

Dietary supplementation with creatine monohydrate prevents corticosteroid-induced attenuation of growth in young rats

Corticosteroids are used as chemotherapeutic agents in many medical conditions, despite many common and potentially serious side effects. Supplementation with creatine monohydrate (CrM) can increase strength and lean body mass in humans and, therefore, may be a viable countermeasure to the side effects of corticosteroids. Therefore, the purpose of this study was to determine if CrM could prevent the attenuation of growth associated with corticosteroid administration. Forty male Sprague-Dawley rats were randomized to the following groups: control (CON, n = 10), 7 mg methylprednisolone x kg(-1) x week(-1) (PRED, n = 10), 2% CrM in diet (CD, n = 10), or CrM and methylprednisolone (CD-PRED, n = 10). Animals received either a weekly sham injection (saline; CON and CD) or an injection of methylprednisolone (PRED and CD-PRED) for 6 weeks. At the completion of the 6th week, body composition was determined and skeletal muscles were collected. Weight gain was attenuated in PRED as compared with all other groups (P < 0.05). Muscle total creatine and phosphocreatine were greater in the extensor digitorum longus in the CD and CD-PRED groups as compared with the CON and PRED groups (P < 0.05); however, total creatine and phosphocreatine in the soleus were not different. Mean fiber area was greater in type II fibers from the extensor digitorum longus in the CD and CD-PRED groups as compared with the CON and PRED groups (P < 0.05); no treatment effect was seen in the soleus. In conclusion, CrM supplementation prevented the attenuation of growth associated with corticosteroids and also increased type II muscle fiber area. These results could have important clinical implications for several patient populations commonly treated with corticosteroids, and further work is required to determine the specific mechanisms underlying the physiological effects that were observed.     

Compensatory adrenal growth in dexamethasone treated rats

The changes in right adrenal weight and adrenocortical mitotic activity have been quantified in the early (up to 72 h) stages following left adrenalectomy or sham adrenalectomy in adult male Sprague Dawley rats. These have been compared with the changes seen in rats pretreated for 14 days with a daily intraperitoneal injection of the synthetic glucocorticoid, dexamethasone (200 micrograms/kg) body weight. The results indicate a significant proliferative response in both groups of animals, although basal proliferative activity and the amplitude of the response was lower in the dexamethasone treated animals. In addition, they suggest two waves of mitotic activity at 24 and 72 h.