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O Ljungqvist

Publications and source records attributed to O Ljungqvist.

At least 19 recordsLinked to original sources
PubMed2000

Exercise induces isoform-specific increase in 5'AMP-activated protein kinase activity in human skeletal muscle.

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.

Adenosine Triphosphate↗
PubMed2000

The hyperinsulinaemic-euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects.

To examine the reproducibility of the hyperinsulinaemic-euglycaemic clamp technique at mid-physiological hyperinsulinaemia, seven healthy subjects ¿age 50 (25, 59) years [median (range)], body mass index 23.1 (20.8, 25.5) kg.m(-2)¿ were investigated with three 2 h hyperinsulinaemic (60 micromol.l(-1))-euglycaemic (4.5 mmol.l(-1)) clamps performed 48 h and 14 days apart respectively. The third clamp was prolonged to 8 h in order to examine effects on glucose disposal during prolonged clamps. The glucose infusion rates (GIRs) during the three 2 h clamps were 7.41 (4.28, 10.96), 7.26 (5.38, 11. 02) and 6.63 (4.42, 10.3) mg.kg(-1).min(-1), with a median intra-individual coefficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly variable gradual increase in GIR was observed, reaching a plateau between 4 and 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P<0.05). This increase was correlated inversely with the GIR between 1 and 2 h (r=-0.82; P<0.05), and directly with age (r=0.86; P<0.05). Carbohydrate oxidation measured by indirect calorimetry was stable during the repeated 2 h clamps and the 8 h clamp. Endogenous glucose production measured by infusion of [6, 6-(2)H(2)]glucose was suppressed during the 8 h clamp. The 2 h hyperinsulinaemic-euglycaemic clamp is reproducible at a mid-physiological range of hyperinsulinaemia. If prolonged, it results in a delayed increase in non-oxidative glucose disposal, which is most pronounced in subjects with low insulin sensitivity. The findings underline the importance of selecting age-matched controls in studies of insulin resistance.

Adult↗
PubMed1999

Post-operative effects on insulin resistance and specific tension of single human skeletal muscle fibres.

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 fibres following 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 single fibres 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 specific tension or a loss of myofibrillar proteins. Other potential cellular mechanisms underlying post-operative weakness are discussed.

Abdomen↗
PubMed1999

Preoperative oral carbohydrates and postoperative insulin resistance.

UNLABELLED: Infusions of carbohydrates before surgery have been shown to reduce postoperative insulin resistance. Presently, we investigated the effects of a carbohydrate drink, given shortly before surgery, on postoperative insulin sensitivity. METHODS: Insulin sensitivity and glucose turnover ([6, 6,(2)H(2)]-D-glucose) were measured using hyper-insulinemic, normoglycemic clamps before and after elective surgery. Sixteen patients undergoing total hip replacement were randomly assigned to preoperative oral carbohydrate administration (CHO-H, n = 8) or the same amount of a placebo drink (placebo, n = 8) before surgery. Insulin sensitivity was measured before and immediately after surgery. Patients undergoing elective colorectal surgery were studied before surgery and 24 h postoperatively (CHO-C (n = 7), and fasted (n = 7), groups). The fasted group underwent surgery after an overnight fast. In both studies, the CHO groups received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation (100g carbohydrates), as well as another 400 ml (50g carbohydrates) 2 h before the initiation of anesthesia. RESULTS: Immediately after surgery, insulin sensitivity was reduced 37% in the placebo group (P < 0.05 vs. preoperatively) while no significant change was found in the CHO-H group (-16%, p = NS). During clamps performed 24h postoperatively, insulin sensitivity and whole-body glucose disposal was reduced in both groups, but the reduction was greater compared to that in the CHO-C group (-49 +/- 6% vs. -26 +/- 8%, P>> 0.05 fasted vs. CHO-C). CONCLUSIONS: Patients given a carbohydrate drink shortly before elective surgery displayed less reduced insulin sensitivity after surgery as compared to patients undergoing surgery after an overnight fast.

Administration, Oral↗
PubMed1999

Insulin resistance: a marker of surgical stress.

Elective surgery causes a marked, transient reduction in insulin sensitivity. The degree of the reduction is related to the magnitude of the operation. The type and duration of surgery performed, perioperative blood loss, and also the degree of postoperative insulin resistance have significant influences on the length of hospital stay. A novel approach to minimize insulin resistance after surgery is being presented and suggests that simply pretreating the elective surgical patient with sufficient amounts of carbohydrates instead of fasting can significantly reduce postoperative insulin resistance. It is not clear which mediators are the most important for the development of insulin resistance after surgery. Nevertheless, marked insulin resistance can develop after elective surgery without concomitant elevations in cortisol, catecholamines or glucagon. The main sites for insulin resistance seem to be extrahepatic tissues, probably skeletal muscle, where preliminary data suggest that the glucose transporting system is involved.

Animals↗
PubMed1999

Surgery-induced insulin resistance in human patients: relation to glucose transport and utilization.

To investigate the underlying molecular mechanisms for surgery-induced insulin resistance in skeletal muscle, six otherwise healthy patients undergoing total hip replacement were studied before, during, and after surgery. Patients were studied under basal conditions and during physiological hyperinsulinemia (60 microU/ml). Biopsies of vastus lateralis muscle were used to measure GLUT-4 translocation, glucose transport, and glycogen synthase activities. Surgery reduced insulin-stimulated glucose disposal (P < 0.05) without altering the insulin-stimulated increase in glucose oxidation or suppression of endogenous glucose production. Preoperatively, insulin infusion increased plasma membrane GLUT-4 in all six subjects (P < 0.05), whereas insulin-stimulated GLUT-4 translocation only occurred in three patients postoperatively (not significant). Moreover, nonoxidative glucose disposal rates and basal levels of glycogen synthase activities in muscle were reduced postoperatively (P < 0.05). These findings demonstrate that peripheral insulin resistance develops immediately postoperatively and that this condition might be associated with perturbations in insulin-stimulated GLUT-4 translocation as well as nonoxidative glucose disposal, presumably at the level of glycogen synthesis.

Arthroplasty, Replacement, Hip↗
PubMed1999

Exercise and insulin cause GLUT-4 translocation in human skeletal muscle.

Studies in rodents have established that GLUT-4 translocation is the major mechanism by which insulin and exercise increase glucose uptake in skeletal muscle. In contrast, much less is known about the translocation phenomenon in human skeletal muscle. In the current study, nine healthy volunteers were studied on two different days. On one day, biopsies of vastus lateralis muscle were taken before and after a 2-h euglycemic-hyperinsulinemic clamp (0.8 mU. kg(-1). min(-1)). On another day, subjects exercised for 60 min at 70% of maximal oxygen consumption (VO(2 max)), a biopsy was obtained, and the same clamp and biopsy procedure was performed as that during the previous experiment. Compared with insulin treatment alone, glucose infusion rates were significantly increased during the postexercise clamp for the periods 0-30 min, 30-60 min, and 60-90 min, but not during the last 30 min of the clamp. Plasma membrane GLUT-4 content was significantly increased in response to physiological hyperinsulinemia (32% above rest), exercise (35%), and the combination of exercise plus insulin (44%). Phosphorylation of Akt, a putative signaling intermediary for GLUT-4 translocation, was increased in response to insulin (640% above rest), exercise (280%), and exercise plus insulin (1,000%). These data demonstrate that two normal physiological conditions, moderate intensity exercise and physiological hyperinsulinemia approximately 56 microU/ml, cause GLUT-4 translocation and Akt phosphorylation in human skeletal muscle.

Adult↗
PubMed1998

Lack of neurohumoral response to pneumoperitoneum for laparoscopic cholecystectomy.

BACKGROUND: Pneumoperitoneum (PP) for laparoscopic surgery induces prompt changes in circulatory parameters. The rapid onset of these changes suggests a reflex origin, and the present study was undertaken to evaluate whether release of vasopressor substances could be responsible for these alterations. The influence of two different anesthesia techniques was also evaluated. METHODS: American Society of Anesthesiologists (ASA) class I patients, scheduled for laparoscopic cholecystectomy, were investigated. The first group (n = 10) was anesthetized intravenously. The second group (n = 6) had inhalation anesthesia. Plasma vasopressin, catecholamines, and plasma renin activity were investigated as neurohumoral vasopressor markers of circulatory stress. The general stress response to surgery was assessed by analysis of plasma cortisol. RESULTS: Induction of pneumoperitoneum caused no apparent activation of vasopressor substances, although several hemodynamic parameters responded promptly. CONCLUSION: The hemodynamic alterations, seen at the establishment of PP during stable anesthesia, cannot be explained by elevation of vasopressor substances in circulating blood.

Adolescent↗
PubMed1998

Bulking fibre prevents translocation to mesenteric lymph nodes of an efficiently translocating Escherichia coli strain in rats.

BACKGROUND: starvation for 24 h prior to experimental haemorrhage increases bacterial translocation in rats. Forty-eight hours starvation alone causes pronounced microbiological changes in caecal contents and a marked increase in bacterial adherence to caecal epithelium. The aim of the present study was to examine whether bulking fibre prevents these microbiological changes induced by starvation, i.e. mucosal adherence and/or bacterial translocation with and without haemorrhage in rats. METHODS: 32 rats were inoculated with the translocating Escherichia coli strain Kl-C1. Groups of these rats were then starved for 48 h with or without access to bulking fibre. An additional group of rats was given bulking fibre and subjected to haemorrhage. A control group was untreated and given regular food. Samples were taken from caecal contents, caecal epithelium, mesenteric lymph nodes and blood. A biochemical fingerprinting method was used to characterize and compare E. coli strains in all samples. RESULTS: ingestion of bulking fibre alone for 48 h significantly reduced the frequency of Kl-C1 both in caecal contents and on caecal epithelium and completely prevented translocation of the strain, compared to starvation without bulking fibre for 48 h. Enforced stress (haemorrhage) increased bacterial translocation to the same level as starvation for 48 h. E. coli phenotypes found in mesenteric lymph nodes were also found adhering to the caecal epithelium. CONCLUSIONS: The presence of bulking fibre in gut lumen, by unknown mechanisms, reduces the frequency of an inoculated translocating strain of E. coli in caecal contents and on caecal epithelium and prevents its translocation to mesenteric lymph nodes.

Animals↗
PubMed1998

Preoperative oral carbohydrate administration reduces postoperative insulin resistance.

UNLABELLED: Infusions of carbohydrates before surgery reduce postoperative insulin resistance. We in-vestigated the effects of a carbohydrate drink, given shortly before surgery, on postoperative metabolism. METHOD: Insulin sensitivity, glucose turnover ([6,6, 2H2]-D-glucose) and substrate utilization were measured using hyperinsulinemic normoglycemic clamps and indirect calorimetry in two matched groups of patients before and after elective colorectal surgery. The drink group (n = 7) received 800 ml of an isoosmolar carbohydrate rich beverage the evening before the operation (100 g carbohydrates), as well as another 400 ml (50 g carbohydrates) 2 h before the initiation of anesthesia. The fasted group (n = 7) was operated after an overnight fast. RESULTS: After surgery, energy expenditure increased in both groups. Endogenous glucose production was higher after surgery and the difference was significant during low insulin infusion rates in both groups (P < 0.05). The supressibility of endogenous glucose production by the two step insulin infusion was similar pre-and postoperatively in both groups. At the high insulin infusion rate postoperatively, whole body glucose disposal was more reduced in the fasted group (-49 +/- 6% vs -26 +/- 8%, P < 0.05 vs drink). Furthermore, during high insulin infusion rates, glucose oxidation decreased postoperatively only in the fasted group (P < 0. 05) and postoperative levels of fat oxidation were greater in the fasted group (P < 0.05 vs drink). Only minor postoperative changes in cortisol and glucagon were found and no differences were found between the treatment groups. CONCLUSIONS: Patients given a carbohydrate drink shortly before elective colorectal surgery displayed less reduced insulin sensitivity after surgery as compared to patients who were operated after an overnight fast.

Adolescent↗
PubMed1998

Vectorcardiographic changes as predictors of cardiac complications during major vascular surgery.

OBJECTIVE: To elucidate the relation of changes in computerized vectorcardiographic trend parameters indicating perioperative myocardial ischemia with perioperative cardiac complications. DESIGN: Prospective clinical study. SETTING: A single university hospital. PARTICIPANTS: Thirty-eight patients undergoing elective abdominal aortic surgery. INTERVENTIONS: Computerized vectorcardiography recorded during surgery and for 48 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Vectorcardiographic spatial alterations in the QRS complex (QRS-VD) and absolute (ST-VM) and spatial (STC-VM) ST-segment changes, previously used indicators of myocardial ischemia, were analyzed and related to the cardiac events detected clinically. In five patients with clearly ischemic (cardiac death, myocardial infarction, recurrent ischemia) and eight patients with possibly ischemic (congestive heart failure, arrhythmia) perioperative cardiac events, ST-VM and STC-VM were significantly increased intraoperatively. Postoperatively, these differences remained, but QRS-VD were also significantly increased. Intraoperative and postoperative changes indicating ischemia were strongly related (r = 0.83). The signs of ischemia were most pronounced during the postoperative 12 to 36 hours. The presence of 60 minutes of signs of ischemia during 2 hours revealed high sensitivity (85%), specificity (80%), and positive (69%) and negative (91%) predictive values for subsequent cardiac events. Traditional vector loop analysis showed signs of non-Q-wave infarctions in six patients, whereas only three of these were detected using standard clinical methods. CONCLUSIONS: Vectorcardiographic signs of myocardial ischemia were significantly increased intraoperatively, but most pronounced postoperatively in the patients subsequently suffering cardiac events. The changes could be related to the individual cardiac morbidity with acceptable precision. Thus, continuous vectorcardiographic monitoring may be beneficial for patients at risk of developing perioperative ischemia.

Aged↗
PubMed1998

Pneumoperitoneum for laparoscopic cholecystectomy is not associated with compromised splanchnic circulation.

OBJECTIVE: To investigate the influence of increased intra-abdominal pressure during pneumoperitoneum on splanchnic circulation. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: Five otherwise healthy patients (mean age of 34 years), undergoing laparoscopic cholecystectomy. INTERVENTIONS: Arterial and hepatic vein catheterization and simultaneous arterial and hepatic vein blood gas sampling in the awake state, during anaesthesia, after the establishment of pneumoperitoneum (intra-abdominal pressure level 11-13 mmHg) and after 30 and 60 minutes of pneumoperitoneum. MAIN OUTCOME MEASURES: Hepatic blood flow was estimated by the continuous infusion method and used as a measure of splanchnic blood flow. Splanchnic oxygen consumption was calculated according to the Fick principle. RESULTS AND CONCLUSION: Splanchnic blood flow and splanchnic oxygen consumption were not affected by pneumoperitoneum at this level of intra-abdominal pressure.

Abdomen↗
PubMed1998

Perioperative oral nutrition.

Much attention has been paid to perioperative intravenous nutrition and postoperative enteral nutrition but the literature concerning perioperative oral nutrition is sparse. This review will draw attention to new ideas about preoperative feeding instead of overnight fasting, it will show that immediate postoperative oral nutrition is tolerated in significant amounts, that liquid supplements may be given routinely after elective surgery, and that it is worth giving dietary advice to malnourished patients on discharge from hospital.

Administration, Oral↗
PubMed1998

Extracellular-regulated protein kinase cascades are activated in response to injury in human skeletal muscle.

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.

Biopsy, Needle↗
PubMed1998

Perioperative insulin and glucose infusion maintains normal insulin sensitivity after surgery.

Elective surgery was performed after overnight fasting, a routine that may affect the metabolic response to surgery. We investigated the effects of insulin and glucose infusions before and during surgery on postoperative substrate utilization and insulin sensitivity. Seven patients were given insulin and glucose infusions 3 h before and during surgery (insulin group), and a control group of six patients underwent surgery after fasting overnight. Insulin sensitivity and glucose kinetics (D-[6,6-2H2]glucose) were measured before and immediately after surgery using a hyperinsulinemic, normoglycemic clamp. Glucose infusion rates and whole body glucose disposal decreased after surgery in the control group (-40 and -29%, respectively), whereas no significant change was found in the insulin group (+16 and +25%). Endogenous glucose production remained unchanged in both groups. Postoperative changes in cortisol, glucagon, fat oxidation, and free fatty acids were attenuated in the insulin group (vs. control). We conclude that perioperative insulin and glucose infusions minimize the endocrine stress response and normalize postoperative insulin sensitivity and substrate utilization.

Arthroplasty, Replacement, Hip↗
PubMed1998

Postoperative induction of insulin-like growth factor binding protein-3 proteolytic activity: relation to insulin and insulin sensitivity.

Increased serum insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) proteolytic activity (IGFBP-3-PA) has been demonstrated in a number of clinical states of insulin resistance, including severe illness, after surgery, and in noninsulin-dependent diabetes mellitus. In the present study we assessed the role of insulin sensitivity in expression of IGFBP-3-PA in serum. In 18 patients studied, a significant increase in IGFBP-3-PA (P < 0.005) was demonstrated after colo-rectal surgery. Eight patients receiving an oral glucose load before surgery demonstrated a significant greater relative increase in IGFBP-3-PA compared with 10 patients not receiving glucose (32.9 +/- 7.1% vs. 8.6 +/- 6.7%, respectively; P < 0.05). Both groups had reduced insulin sensitivity after surgery (-58 +/- 4%; P < 0.0001; n = 18), as determined by hyperinsulinemic, normoglycemic clamps; however, the group not receiving glucose displayed 18% less insulin sensitivity than the oral glucose load group (P < 0.05). Multiple regression analysis demonstrated that the relative changes in IGFBP-3-PA and C peptide levels were inversely correlated (P < 0.05), suggesting that increased IGFBP-3-PA, presumably increasing IGF bioavailability, may be associated with decreased insulin demands. Interestingly, insulin infusion during the 4-h hyperinsulinemic, normoglycemic clamp performed 24 h after surgery (post-op) resulted in a further increase in IGFBP-3-PA in both groups (P < 0.005), whereas no significant responses could be demonstrated during the pre-op clamp. The expression of increased IGFBP-3-PA was accompanied by conversion of endogenous intact 39/42-kDa IGFBP-3 into its 30-kDa fragmented form as determined by Western immunoblotting, and this conversion was virtually complete after the 4-h post-op clamp in patients displaying marked increases in IGFBP-3-PA. Characterization of the IGFBP-3-PA demonstrated that it was specific for IGFBP-3, as no degradation of IGFBP-1 and -2 was detected, and the use of various protease inhibitors demonstrated that serine proteases and possibly matrix metalloproteinases contribute to the increased IGFBP-3-PA level after surgery. We propose that IGF bioavailability may be increased by the induction of IGFBP-3-PA in insulin-resistant subjects, and that insulin regulates IGFBP-3-PA in this state.

Administration, Oral↗