1.
Aronson, D., et al.
(författare)
Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle
1998
Ingår i: American Journal of Physiology. - : HighWire Press. - 0002-9513 .- 2163-5773. ; 275:2, s. C555-C561
Tidskriftsartikel (refereegranskat) abstract
The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. However, it is not known whether these signaling cascades also participate in the response to injury in human tissues. To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing.
2.
Balagopal, P., et al.
(författare)
Skeletal muscle heavy-chain synthesis rate in healthy humans
1997
Ingår i: American Journal of Physiology. - : HighWire Press. - 0002-9513 .- 2163-5773. ; 272:1, s. 45-50
Tidskriftsartikel (refereegranskat) abstract
Mixed muscle protein synthetic rate has been measured in humans. These measurements represent the average of synthetic rates of all muscle proteins with variable rates. We determined to what extent the synthesis rate of mixed muscle protein in humans reflects that of myosin heavy chain (MHC), the main contractile protein responsible for the conversion of ATP to mechanical energy as muscle contraction. Fractional synthetic rates of MHC and mixed muscle protein were measured from the increment of [C-13]leucine in these proteins in vastus lateralis biopsy samples taken at 5 and 10 h during a primed continuous infusion of L-[1-C-13]leucine in 10 young healthy subjects. Calculations were done by use of plasma [C-13]ketoisocaproate (KIC) and muscle tissue fluid [C-13]leucine as surrogate measures of leucyl-tRNA. Fractional synthetic rate of MHC with plasma KIC (0.0299 +/- 0.0043%/h) and tissue fluid leucine (0.0443 +/- 0.0056%/h) were only 72 +/- 3% of that of mixed muscle protein (0.0408 +/- 0.0032 and 0.0603 +/- 0.0059%/h, respectively, with KIC and tissue fluid leucine). Contribution of MHC (7 +/- 1 mg . kg(-1) . h(-1)) to synthetic rates of whole body mixed muscle protein (36 +/- 5 mg . kg(-1) . h(-1)) and whole body protein (127 +/- 4 mg . kg(-1) . h(-1)) is only 18 +/- 1 and 5 +/- 1%, respectively. This relatively low contribution of MHC to whole body and mixed muscle protein synthesis warrants direct measurement of synthesis rate of MHC in conditions involving abnormalities of muscle contractile function.
3.
Bark, Tor, et al.
(författare)
Food deprivation increases bacterial translocation after non-lethal haemorrhage in rats
1995
Ingår i: European Journal of Surgery. - : Taylor & Francis Scandinavia. - 1102-4151 .- 1741-9271. ; 161:2, s. 67-71
Tidskriftsartikel (refereegranskat) abstract
OBJECTIVE:To investigate whether brief fasting before the induction of hypotension by non-lethal haemorrhage may induce translocation of enteric bacteria to mesenteric lymph nodes or blood in rats.DESIGN:Laboratory experiment.SETTING:University departments of surgery and microbiology, Sweden.MATERIAL:39 Male Sprague-Dawley rats.INTERVENTIONS:20 animals were fasted for 24 hours, all 39 then underwent controlled haemorrhage for 60 minutes that reduced the blood pressure to 55 mm Hg.MAIN OUTCOME MEASURES:Differences in blood loss, blood glucose concentrations, and packed cell volume; and aerobic cultures of mesenteric lymph nodes and blood.RESULTS:Fasted rats (n = 20) lost 2.3% of blood volume compared with 2.8% in fed rats(p < 0.001). Packed cell volume dropped by 11.3% in fasted rats and 16.5% in fed rats (p < 0.001). Glucose concentrations rose by 7.0 mmol/l in fasted rats compared with 21.0 mmol/l in fed rats (p < 0.001). Mesenteric lymph nodes contained enteric bacteria in 14/20 fasted rats compared with 6/19 fed rats (p < 0.05). In 4 fasted rats blood cultures grew pathogenic bacteria compared with no fed rats (p = 0.11). The number of bacteria found in mesenteric lymph nodes was significantly greater in fasted than in fed rats (p = 0.01).CONCLUSIONS:Brief fasting before hypotension caused by non-lethal haemorrhage was associated with significantly increased bacterial translocation compared with fed animals. Increases in blood glucose concentrations and plasma refill may have had a protective effect in fed rats. These experiments may be of clinical relevance as elective operations are usually preceded by overnight fasting.
4.
Bark, Tor, et al.
(författare)
Glutamine supplementation does not prevent bacterial translocation after non-lethal haemorrhage in rats
1995
Ingår i: European Journal of Surgery. - : Taylor & Francis Scandinavia. - 1102-4151 .- 1741-9271. ; 161:1, s. 3-8
Tidskriftsartikel (refereegranskat) abstract
OBJECTIVE:To find out whether supplementation of an enteral diet with glutamine would reduce translocation of bacteria to mesenteric lymph nodes or blood after major haemorrhage in rats.DESIGN:Open randomised study.SETTING:University departments of surgery and microbiology, Sweden.MATERIAL:49 Sprague-Dawley rats.INTERVENTIONS:Rats were fed enterally for 7 days on diets supplemented with either glutamine or an isonitrogenous amount of non-essential amino acids. After feeding, 8 experimental and 8 control rats underwent sham operation; 9 and 7, respectively, underwent moderate haemorrhage (to 65 mm Hg); and 9 and 8, respectively, underwent severe haemorrhage (50 mm Hg) without reinfusion.MAIN OUTCOME MEASURES:Microbiological analyses of samples of blood and mesenteric lymph nodes taken 24 hours after haemorrhage.RESULTS:The median (interquartile) number of colony forming units/mesenteric lymph nodes after moderate haemorrhage in animals who were given glutamine supplementation was 11 (0-34) and in control animals 20 (0-178). After severe haemorrhage the corresponding figures were 199 (10-310) and 22 (0-187). No pathogens were isolated from blood cultures.CONCLUSION:Glutamine supplementation before haemorrhage did not reduce bacterial translocation to mesenteric lymph nodes in this rat model.
5.
Boija, Per Olov, et al.
(författare)
Hypovolaemic stress induced glycogenolysis, isolated liver perfusion study
1987
Ingår i: Research in experimental medicine. - : Springer. - 0300-9130 .- 1433-8580. ; 187:5, s. 315-322
Tidskriftsartikel (refereegranskat) abstract
Intrinsic hepatic glycogenolysis was examined after hypovolemic stress. Hemorrhagic hypotension of 70 (P70) and 40 mm Hg (P40) for 60 min was inflicted for two postprandial groups and of 70 mm Hg (S70) in a 24-h starved group. The results were compared with three control groups; one postprandial (Pc), one 24-h starved (Sc), and one starved for 9 h (Sc: 9) to mimic the glycogen depletion produced by 70 mm Hg hemorrhagic hypotension. Glucose output was studied in vitro using av recirculating isolated liver perfusion system with a perfusate free of glucose and endocrine stimulation. Liver glycogen determination was made before perfusion start. Although the glycogen stores were decreased after hemorrhage glucose yield was increased (P70) and unchanged (P40) as compared to controls (Pc and Sc: 9). Both starved groups delivered small amounts of glucose, but the released fraction of the S70 group was more than twice that from the Sc group. These data suggest a liver enzyme activation with increased velocity of the enzymesubstrate reactions responsible for glycogen degradation, induced during in vivo hemorrhage and persisting for at least 30 min in vitro perfusion.
6.
Degens, Hans, et al.
(författare)
Post-operative effects on insulin resistance and specific tension of single skeletal muscle fibres
1999
Ingår i: Clinical Science. - : Lippincott Williams & Wilkins. - 0143-5221 .- 1470-8736. ; 97:4, s. 449-455
Tidskriftsartikel (refereegranskat) abstract
Surgery and accidental trauma are associated with a transient period of insulin resistance, substrate catabolism and muscle weakness. In the present study, we evaluated the changes in the force-generating capacity of chemically skinned single muscle fibresfollowing abdominal surgery. Biopsies of the m. vastus lateralis were obtained in three patients 1 day before and 3 or 6 days after surgery. Part of the biopsy was frozen for histochemical analysis of the fibre cross-sectional area (FCSA) and myofibrillar protein content, and another part was used for single-fibre contractile measurements. All patients developed insulin resistance following surgery. The maximum velocity of unloaded shortening of single muscle fibres did not change following surgery. The FCSA did not decrease after surgery, as determined either from histochemical sections or from singlefibres measured at a fixed sarcomere length of 2.76+/-0.09 microm (mean+/-S.D.). Further, the force-generating capacity of the single fibres, measured as maximal Ca(2+)-activated force (P(0)) or as P(0) normalized to FCSA (specific tension), remained unchanged, as did the myofibrillar protein content of the muscle. In conclusion, the muscle weakness associated with post-operative insulin resistance is not related to a decreased specifictension or a loss of myofibrillar proteins. Other potential cellular mechanisms underlying post-operative weakness are discussed.
7.
Esahili, A. H., et al.
(författare)
Twenty-four hour fasting increases endotoxin lethality in the rat
1991
Ingår i: European Journal of Surgery. - 1102-4151 .- 1741-9271. ; 157:2, s. 89-95
Tidskriftsartikel (refereegranskat) abstract
The effect of 24 h food deprivation on endotoxin (ET) lethality in SpD rats was studied. Fed and fasted animals received either 6 h i.v. infusions or i.p. boluses of ET at low, intermediate and high doses, and survival for seven days observed. Fasting was associated with 208-240% greater mortality when ET was infused i.v., and 87-200% when given i.p. ET doses LD10-LD80 gave a linear relationship with mortality. In non-fasted control rats liver glycogen content reduced by 1.28 mumols/min/g dry liver wt over the first post-prandial six hours, and increased by 65-99% in a dose dependent manner after ET (p less than 0.01). Evidence was also obtained relating both liver damage (assessed blind by histopathological scoring) and leucopenia with endotoxin dose, results which were modified by nutritional status. The evidence supports the role of liver glycogen as a protective substrate resource in endotoxic shock.
8.
Essén, Pia, et al.
(författare)
Laparoscopic cholecystectomy does not prevent the postoperative protein catabolic response in muscle
1995
Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 222:1, s. 36-42
Tidskriftsartikel (refereegranskat) abstract
OBJECTIVE:The authors determined the effect of laparoscopic cholecystectomy on protein synthesis in skeletal muscle. In addition to a decrease in muscle protein synthesis, after open cholecystectomy, the authors previously demonstrated a decrease in insulin sensitivity. This study on patients undergoing laparoscopic and open surgery, therefore, included simultaneous measurements of protein synthesis and insulin sensitivity.SUMMARY BACKGROUND DATA:Laparoscopy has become a routine technique for several operations because of postoperative benefits that allow rapid recovery. However, its effect on postoperative protein catabolism has not been characterized. Conventional laparotomy induces a drop in muscle protein synthesis, whereas degradation is unaffected.METHODS:Patients were randomized to laparoscopic or open cholecystectomy, and the rate of protein synthesis in skeletal muscle was determined 24 hours postoperatively by the flooding technique using L-(2H5)phenylalanine, during a hyperinsulinemic normoglycemic clamp to assess insulin sensitivity.RESULTS:The protein synthesis rate decreased by 28% (1.77 +/- 0.11%/day vs. 1.26 +/- 0.08%/day, p < 0.01) in the laparoscopic group and by 20% (1.97 +/- 0.15%/day vs. 1.57 +/- 0.15%/day, p < 0.01) in the open cholecystectomy group. In contrast, the fall in insulin sensitivity after surgery was lower with laparoscopic (22 +/- 2%) compared with open surgery (49 +/- 5%).CONCLUSIONS:Laparoscopic cholecystectomy did not avoid a substantial decline in muscle protein synthesis, despite improved insulin sensitivity. The change in the two parameters occurred independently, indicating different mechanisms controlling insulin sensitivity and muscle protein synthesis.
9.
Fujii, N., et al.
(författare)
Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle
2000
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - San Diego, CA, USA : Academic Press. - 0006-291X .- 1090-2104. ; 273:3, s. 1150-1155
Tidskriftsartikel (refereegranskat) abstract
The 5'AMP-activated protein kinase (AMPK) is stimulated by contractile activity in rat skeletal muscle. AMPK has emerged as an important signaling intermediary in the regulation of cell metabolism being linked to exercise-induced changes in muscle glucose and fatty acid metabolism. In the present study, we determined the effects of exercise on isoform-specific AMPK activity (alpha1 and alpha2) in human skeletal muscle. Needle biopsies of vastus lateralis muscle were obtained from seven healthy subjects at rest, after 20 and 60 min of cycle ergometer exercise at 70% of VO(2)max, and 30 min following the 60 min exercise bout. In comparison to the resting state, AMPK alpha2 activity significantly increased at 20 and 60 min of exercise, and remained at a higher level with 30 min of recovery. AMPK alpha1 activity tended to slightly decrease with 20 min of exercise at 70%VO(2)max; however, the change was not statistically significant. AMPK alpha1 activities were at basal levels at 60 min of exercise and 30 min of recovery. On a separate day, the same subjects exercised for 20 min at 50% of VO(2)max. Exercise at this intensity did not change alpha2 activity, and similar to exercise at 70% of VO(2)max, there was no significant change in alpha1 activity. In conclusion, exercise at a higher intensity for only 20 min leads to increases in AMPK alpha2 activity but not alpha1 activity. These results suggest that the alpha2-containing AMPK complex, rather than alpha1, may be involved in the metabolic responses to exercise in human skeletal muscle.
10.
Goodyear, Laurie J.L, et al.
(författare)
Glucoseingestion causes GLUT4 translocation in human skeletal muscle
1996
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 45:8, s. 1051-1056
Tidskriftsartikel (refereegranskat) abstract
In humans, ingestion of carbohydrates causes an increase in blood glucose concentration, pancreatic insulin release, and increased glucose disposal into skeletal muscle. The underlying molecular mechanism for the increase in glucose disposal in human skeletal muscle after carbohydrate ingestion is not known. We determined whether glucoseingestion increases glucose uptake in human skeletal muscle by increasing the number of glucose transporter proteins at the cell surface and/or by increasing the activity of the glucose transporter proteins in the plasma membrane. Under local anesthesia, approximately 1 g of vastus lateralis muscle was obtained from six healthy subjects before and 60 min after ingestion of a 75-g glucose load. Plasma membranes were isolated from the skeletal muscle and used to measure GLUT4 and GLUT1 content and glucosetransport in plasma membrane vesicles. Glucose ingestion increased the plasma membrane content of GLUT4 per gram muscle (3,524 +/- 729 vs. 4,473 +/- 952 arbitrary units for basal and 60 min, respectively; P < 0.005). Transporter-mediated glucosetransport into plasma membrane vesicles was also significantly increased (130 +/- 11 vs. 224 +/- 38 pmol.mg-1.s-1; P < 0.017), whereas the calculated ratio of glucose transport to GLUT4, an indication of transporter functional activity, was not significantly increased 60 min after glucose ingestion (2.3 +/- 0.4 vs. 3.0 +/- 0.5 pmol.GLUT4 arbitrary units-1.s-1; P < 0.17). These results demonstrate that oral ingestion of glucose increases the rate of glucose transport across the plasma membrane and causes GLUT4 translocation in human skeletal muscle. These findings suggest that under physiological conditions the translocation of GLUT4 is an important mechanism for the stimulation of glucose uptake in human skeletal muscle.
